What is Good Youtube Its Your Boy Chris On the Mic and Today I'll Be Showing You
guys the comparison between NBA 2k17 and 2k18 to show you guys the differences
between the two games graphically just yesterday NBA 2k Studios released some
screenshots of their latest game NBA 2k from there we can see in game action
Paul George DeMar DeRozan and Isiah Thomas the 2k 17
gameplay I'll be showing you will be on the corner and it's from our ps4 there
if you guys really enjoyed this video please like it first off I want to thank
you for making it to the end of this video and second of all if you guys want
For more infomation >> NBA 2K18 vs NBA 2K17 Gameplay Comparison🔥 - First Screenshots Released!!(BETTER OR WORSE) - Duration: 2:01.-------------------------------------------
#TechTuesday Chat: Anchor OR LiveLeap -- YOU DECIDE! #31DaysLIVE Day 21 - Duration: 41:07.
For more infomation >> #TechTuesday Chat: Anchor OR LiveLeap -- YOU DECIDE! #31DaysLIVE Day 21 - Duration: 41:07. -------------------------------------------
EASIEST SLIME EVER (NO BORAX OR CONTACT SOLUTION) !!! - Duration: 1:55.
And today I am going to make the easiest slime ever
First I am going to put glue (any white glue)
And next we are going to put Persil gel
put a little bit
now we mix it with hands
now we put coloring (optional - food coloring or any water based colors)
Now I am going to make bubbles
The last thing is baby oil ( a little bit to avoid sticking)
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Nintendo Switch: Joy-Con Grip or Pro Controller? - Duration: 6:59.
Hey everybody, it's Akfamilyhome here,
and today we're going to be talking about the Joy-Con!
Nintendo's virtual ice cube simulators that
Nintendo's new controllers for the Switch that as they say, 'give you total gameplay flexibility'.
You can swing them around with motion controls like baby Wii Remotes!
Hold them separately and play while lying in bed!
Give it to another player and watch as they keep taking accidental screenshots with the
capture button!
Or…slot them into the Joy-Con grip, making it become a more traditional controller.
But is it really that traditional considering Nintendo has also released a dedicated Pro
Controller for the Switch that, at first glance, does the exact same thing that the bundled
Joy-Con grip can already accomplish?
Well, not exactly, as there are definitely significant differences between the two, so
without further ado, let's begin comparing their PROS and CONS.
Ehhhhhh?
Thank you, thank you, have a great night
Keep in mind, I'm not taking the Joy-Con's functionality when held separately or sideways
into account, as I'm simply pitting the Joy-Con grip layout against the Pro Controller so
that people who aren't sure if they should stick to the Joy-Con grip can learn more about
the differences the Pro Controller offers.
Let's just get the similarities out of the way first.
Both the Joy-Con grip and Pro Controller offer the same buttons: Analog sticks, directional
buttons, ABXY, Plus, Minus, ZL, ZR, L, R, the Capture button and the Home button, as
well as HD Rumble and amiibo functionality.
The only differences here are how some of the buttons are laid out and the presence
of the sandwich eating sensor on the Right Joy-Con.
Okay, you probably already know the obvious differences between the two so I don't really
have to explain how the Plus and Minus buttons are shaped differently or something like that.
Let's just get to the nitty-gritty.
First of all, the Pro Controller definitely has a better button placement than the Joy-Con
grip as it is designed as a traditional controller itself.
With how the Joy-Cons have to be completely vertical, the button placement on the Joy-Con
grip might feel off-putting to some if they're accustomed to a traditional controller.
For me, however, I can use it just fine as a normal controller, the only nitpick being
how the right stick might get in the way when I try to access both the Y and B buttons.
Onto the buttons themselves, they are much larger on the Pro Controller so you might
want to take that into consideration if you have large hands, and the buttons are slightly
less clicky than those of the Joy-Con.
At first I was a bit worried seeing I didn't like the mushy buttons on the DS Lite and
original 2DS, but they're less mushy here and the larger buttons allow me to get a better
grip on the buttons themselves.
The D-Pad on the Pro Controller obviously replaces the directional buttons on the Joy-Con
and works really well.
I've seen some reports about it not registering directions accurately for some people, like
registering left and right as up instead but so far I've had no issues with it.
It's definitely better than the independent buttons on the Joy-Con if you want to play
2D games, but personally, I don't find moving in 2D games that big of a problem on the Joy-Con
becaaause…cue amazingly timed segway into…
The analog sticks!
Now these are probably, in my opinion, one of the biggest differences between the Pro
Controller and Joy-Con grip.
On the Joy-Con grip, due to the need for being portable, the analog stick is pretty tiny
and only travels a short distance.
While it might not be ideal for actual analog movement, it works pretty dang fine in and
of itself, and is even pretty great for 2D movement in sidescrollers as snapping from
one direction to the opposite is quick, just like using an actual D-Pad.
Compared to other options like the directional buttons or the 3DS's Circle Pad, I think that
this is the best analog stick for covering both 3D and 2D movement.
On the Pro Controller the analog stick travel is larger and similar to other traditional
controllers so it's not as good for 2D movement, though that's what the D-Pad is for.
*intermission*
Heyo, uh, I'm just adding this extra bit in here to showcase one of the actual minor issues
I've been having with the Switch Pro Controller, and that is when you quickly flick any of
the analog sticks in one direction, sometimes it registers the opposite direction when it
goes back to the original position.
For example, if I try to flick this analog stick right, you see sometimes the dot on
the screen goes to the left side instead.
And same, for example, when I flick downwards, it sometimes goes back up.
And uh, it's not that big of a deal, like, if I hold it and release it, it doesn't do that,
but when I'm quickly scrolling through menus by flicking the analog stick, sometimes
it goes back to a previous option, so uh it IS kind of annoying and I'm not sure if my
controller is the only one that does this, so leave your comments below, I'm curious
to see if anyone else is experiencing this problem.
So, uh, yeah, that's the only problem I have with it honestly.
*end intermission*
Oh, and let's not forget the shoulder buttons which are definitely larger and more comfortable
on the Pro Controller, especially with the L and R buttons which are basically just thin
strips on the Joy-Con grip.
As a side note, I also wanted to mention that even though HD Rumble is present on both the
Joy-Con grip and Pro Controller, I feel that the effect is definitely much more stronger
and noticeable in the Joy-Con grip, probably because there are two rumble engines in that configuration
instead of one.
As such, rumble effects like the engine revving in Mario Kart 8 Deluxe feel much more enhanced.
Last but not least, the battery life.
The Joy-Con have an estimated battery life of about 20 hours each, and to charge them,
you either have to buy the charging grip or battery pack sold separately, or attach them
to the Switch itself while its charging.
Their battery life is totally adequate but let's be honest, who wants to keep track of
two separate battery meters, am I right?
There IS that slight possibly that one might run out of juice before the other, after all.
And enter the Pro Controller, with a staggering estimated battery life of 40 hours thanks
to it containing basically a 3DS battery.
If you're using it normally, you could probably be able to use it for a month or more after
a single charge.
That's very impressive.
And both the charging Joy-Con grip and Pro Controller charge via USB-C, which is the
cherry on top of the sundae.
So, what's the final verdict?
Well, it goes without saying that if you're going to be playing the Switch in docked mode
a lot, the Pro Controller is obviously the better choice with its great ergonomics, large
buttons and the like.
But to other people, is it worth the 70-dollar asking price when they already have the Joy-Con grip?
Personally, I don't find the Joy-Con grip that bad if you just want something that sorta
resembles a traditional controller, heck, I only got the Pro Controller a few days ago
and was perfectly fine before without it.
But if you're one of those serious, pro players who play for longer times, the bonuses offered
by the Pro Controller are definitely worth it.
And to be honest, a lot of it really comes down to personal preference.
Some people might like the clickier buttons on the Joy-Con, some might prefer larger analog
stick travel, etc.
So in the end, it's really up to you to decide which one is more suited for you based on
the small differences I mentioned, and your regular play style.
Well, that's about it for this video, I hope this can help anyone who's currently on the fence
about upgrading controllers, and I'll catch you guys later when my next major video is complete.
MVBBY.
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Is Insulin Really a Response to Carbohydrate or Just a Gauge of Energy Status? | MWM 2.23 - Duration: 35:18.
Insulin. Is the control of insulin
secretion finally something we've
arrived at that is all about
carbohydrate or is even insulin
secretion mostly just about
cellular energy status?
Find out in today's lesson.
A ketogenic diet has neurological benefits.
Why do we have to eat such
an enormous amount of food?
Complex science.
Clear explanations.
Class is starting now.
Hi. I'm Dr. Chris Masterjohn of
chrismasterjohnphd.com. And you're
watching Masterclass with Masterjohn.
We are now in our 23rd in a series of
lessons on the system of energy metabolism.
And today we are layering in for the first
first time the effects of hormones.
And to begin our discussion of insulin
we're going to talk about what controls
insulin secretion. We still at this point have
been talking about fat versus
carbohydrate, we're not ready yet to
layer in protein because of its
complexity. So although protein effects
insulin secretion, we're going to talk
about it only to a limited extent today and
we're primarily going to focus
on fat versus carbohydrate.
Nevertheless we're going to tackle
what seems like an incredible conflict
between what we know about the
effects of nutrition and what
happens at the cellular level. Because
we know nutritionally that you get more
insulin when you have more carbohydrate
and less when you have less. And yet when
we look at the mechanisms governing energy
secretion in the pancreatic beta-cell,
it seems to be all about energy status.
So let's carve out this problem and show it
exists and then let's try to explain it.
Shown on the screen is the design of a
study looking at the effects of
different meal patterns on insulin and
glucagon. Glucagon is a hormone that
opposes the action of insulin.
Although it's associated with the fasted state,
you also get a lot of glucagon when you
eat things that aren't carbohydrates,
especially protein.
One of the reasons for this is that insulin,
in the case of protein, is taking amino acids
into cells, and if you just had protein
stimulating insulin for that purpose it would
lower your blood sugar. So you need to have the
opposing effect of glucagon to allow
certain functions of insulin and prevent
other functions of insulin that are
undesirable in that context. We'll
talk about that in much more detail when
we get to protein, but for now let's just
take a look at these meals. We have an
oral glucose tolerance test which is a
100% glucose. We have a high-fat
meal that's deriving from fat 72% of
its calories and only 23% from
carbohydrate. We have a high protein
meal that's deriving 64% of its energy
from protein and 26% from
carbohydrate. And we have a mixed meal which
is really the high carbohydrate meal, it's the
meal that is 60% carbs. So all of these
are mixed, but there's more emphasis on fat
versus protein versus carbohydrate.
In this diagram plasma insulin following
the meal is shown on the left and plasma
glucagon is shown on the right. You can
see that the glucose is shown with the
filled in circles and the glucose
produces the most insulin and it
produces the least glucagon. In fact what
you see here is that glucose on its own
not only raises insulin, but it
suppresses glucagon; high insulin and low
glucagon gives you the most activity of
most of the processes downstream from
insulin. In other words a high insulin-to-
glucagon ratio gets you the most insulin
signaling. The mixed meal, which is really
a high carbohydrate meal, is next in line
for high insulin and next in line for
lowest glucagon. You see that protein and
fat both stimulated similar amounts of
insulin, again this is in the context of
a mixed meal where there is carbohydrate
in the meal, but having the predominant
source of calories be protein or fat led
to considerable insulin and considerable
glucagon. For insulin the rise was fairly
similar between the high-fat meal and
the high-protein meal, but the insulin
peaked earlier for the protein meal and
peaked later for the fat meal. And for
glucagon the glucagon was highest in a
high-protein meal and was next highest
in the high-fat meal. So carbohydrate
gives you the highest insulin to
glucagon ratio and the highest absolute
insulin amount, that translates into the
greatest insulin signaling. Contrast this
with what we know about what governs the
secretion of insulin by the pancreatic
beta-cell. Inside the pancreatic beta-cell,
the single most important governor
of insulin secretion is a high ratio of
ATP to ADP. That means that it's the
cellular energy status that is the
central governor of insulin secretion in
the pancreatic beta-cell. This diagram
shows what happens in more detail.
And this is, in the context of a field over
insulin secretion in which there are
many controversies and disagreements,
this right here on the screen is the one
least controversial thing that you will
find as the consensus in any scientific
paper about what triggers insulin
secretion. When you have a low energy
state you have more ADP and less ATP.
This doesn't literally mean that you
have more ADP than ATP,
it just means relative to higher energy
conditions ADP is predominating. And when
you have a low-energy state mediated
through the ADP-to-ATP ratio, this
activates potassium channels in the cell
membrane. Those channels allow potassium
to leave the cell. Potassium is
positively charged, so having those
channels open means a net loss of
positive charge from the inside of the
cell and a net gain of positive charge
outside the cell. This leads to a
polarization of charge across the
membrane. Outside the cell is more
positive in general because of the
potassium, inside the cell is more
negative. When you have a polarization of
charge across the membrane you have a
voltage. You have voltage-sensitive
calcium channels that are blocked when
the membrane is polarized; they're
blocked in response to the voltage
across the membrane. When the calcium
cannot enter the cell, the calcium
concentration inside the cell is low.
Calcium is very frequently used as an
intracellular messenger. A low
concentration of intracellular calcium
ions keeps insulin from being secreted.
Some of that insulin is stored in the
middle of the cell where it's ready to
be moved at a later time; some of that
insulin is right associated with the
inside of the membrane ready to go when
first called. If the energy state of the
beta-cell increases, you get an abundance
of ATP relative to ADP. This change in
the ratio inhibits the potassium
channels.The potassium now cannot get
outside and that depolarizes the
membrane, meaning the polarity across the
membrane of charge, the voltage across
the membrane, now dissipates.
Positive charges can't get out.
So now you have an equilibration
where you have closer to electric
neutrality on each side of the membrane.
Since the calcium channels are sensitive
to the voltage this loss of voltage or
depolarization opens up those calcium
channels. Calcium comes into the cell, the
rise in intracellular calcium stimulates
a cascade of events that lead to insulin
being delivered to the cell membrane
with the vesicles opening up and
allowing insulin to travel outside of
the cell. This idea of changes
in membrane polarization triggering
some other event or cascade
of events, is extremely common in
cellular biology. This is just one
example of a common phenomenon.
So this being the part of insulin secretion that
is not controversial means that what we
know best about insulin secretion is
that it's governed by the amount of ATP
in the pancreatic beta-cell. How can it
be that nutritionally there's a specific
effect of glucose and yet at the level
of molecular biology and biochemistry
it's all about cellular energy status,
it's all about ATP? I believe the answer
is that we cannot explain the specific role
of glucose in insulin signaling by invoking
biochemistry or molecular biology.
I believe instead we need to
invoke anatomy and physiology.
Anatomy is the relationship between the organs
and the other structural features of our
body; physiology is how metabolism is
coordinated between those different
organs to orchestrate some overall net
result in the body that's more than the
sum of its parts. So let's take a look at
the anatomy and physiology of how
carbohydrates and fats would reach
a pancreatic beta-cell.
The pancreas is closely associated with the
organs of the digestive system.
Inside your torso underneath the cavity where
your lungs are, you have the liver,
you have the gallbladder located tucked
into the liver, you have ducts that lead
together into the small intestine,
you have the stomach, and you have that
lead into the small intestine, the first
section of which is the duodenum.
The pancreas is tucked underneath the
stomach relatively close to the liver
and gallbladder, but tucked into the
curve of the duodenum, giving it very close
access to the small intestine.
It's important to realize that glucose or fat
when we first eat it is going to go from
the stomach into the small intestine.
That does not mean at all that they have
direct access to the pancreas. The reason
The pancreas is tucked in with the
duodenum is because it plays a role in
digestion. Its role in responding to
nutrients to secrete insulin is not
related to the direct proximity to the
duodenum. The key role of the pancreas
in the digestive system is to make
digestive enzymes. So we have bile acids that are
made in the liver and come through the
hepatic duct, can be stored in the
gallbladder and come to the cystic duct
into the common bile duct and then the
pancreatic duct takes digestive
secretions from the pancreas, mixes them
with the bile acids and they
get carried into the duodenum so that
they can begin the digestive processes.
If we look inside a pancreas what we
will find is one to two million islets.
An islet is a collection of many cells
involved in hormone secretion, which
constitute the endocrine function of the
pancreas. The islets are surrounded by
circular arrangements of acinar cells in
acini that are responsible for
digestive secretions. These arrange
circularly around the islet and each of
the acini is itself a circle of cells
that can input the digestive secretions
into the middle of those cells to be
carried through the pancreatic duct into
the duodenum.
Inside the islet we have many, many cells.
We have alpha-cells, beta-cells, delta-cells
and F-cells. The alpha-cells make
glucagon, the beta-cells make insulin, the
delta-cells make somatostatin and the F-
cells make pancreatic polypeptide.
Somatostatin and pancreatic polypeptide
play special regulatory roles that are
not of concern to us in this discussion.
We're briefly touching on glucagon here
but we're primarily going to focus on it
once we get to protein. For our purposes
what we care most about is that 70% of
the cells in the islet are beta-cells.
How would carbohydrate and fat reach the
pancreatic beta-cell? Well in fact their
transport is completely different. If you
have carbohydrate coming into the small
intestine, it's going to travel through
the portal vein directly to the liver.
It's going to go to the liver with all the
other water-soluble nutrients in the
diet. That means the liver gets first
access to the carbohydrate. Well that's
important because the first thing you
want to do with carbohydrate is replete
your hepatic glycogen supply because
hepatic glycogen is what keeps your
blood sugar stable between meals. So you
can imagine already that if you're
running low on carbohydrate that in
itself is going to make less
carbohydrate ever reach the pancreas
because it's going to go to the liver
first to replete the glycogen stored
there. The hepatic veins then take
remaining carbohydrate into the inferior
vena cava, which is the vein that's going
to take those nutrients into the heart.
From the heart those nutrients reach the
aorta and they can go through multiple
arteries to either circulate to many
other organs or to go specifically to
the pancreas. By contrast if fats are in
the small intestine they're going to get
packaged into lipoproteins, which are
spherical particles that help them
transport through our system and are
called chylomicrons.
The chylomicrons are going to leave the small
intestine through the thoracic duct,
which is part of the lymphatic system.
These chylomicrons are going to
have long-chain fats and any other
fat-soluble nutrients. These fats are going
to go through the thoracic duct as part
of the chylomicrons and then empty into
the inferior vena cava, which is where
they first reach the circulatory system
and which is the part where they share
in common with the travel of
carbohydrate that had come from the
liver. Like the carbohydrates that came
from the liver, the fat that came from
the lymphatic system that never yet went
into the liver, is going to reach the
heart first; it's going to go through the
aorta; from the aorta it goes through
multiple arteries that can take it to
the pancreas or to the many other
organs. So the two key differences
between carbohydrate and fat so far is
that carbohydrate goes through the
portal vein and the liver has first
access before it ever gets to the heart
or pancreas. Fat goes from the small
intestine through the lymphatic system and
never goes to the liver until after it
goes through the heart, which has first
access, and then to the general
circulation where it can reach the liver
or the pancreas. If we look at how the
fat or carbohydrate would get inside
cells, it gets even more different.
We digest carbohydrate to free sugars.
In the case of starch, for example, we digest
it into glucose, or if we eat glucose we
get free glucose. If we have free glucose,
it transports
right into the cell through the glucose
transporters in the cell membrane.This
is a very simple transport system. The
transport of chylomicrons, of fats
contained in chylomicrons, is quite
different. In certain cells that make the
enzyme lipoprotein lipase, they can send
the enzyme out into the capillary beds
that nourish them. So let's say this is
the heart, the heart cell makes LPL, puts
it out into the capillaries nourishing the
heart. Same thing with the muscle, the
muscle cell makes the LPL sends it out
into the capillary bed. The capillary bed
is made of capillaries and the lumen of
the capillary is the area in which blood
flows. That lumen is enclosed by the
capillary endothelial cells, which make
the lining of the capillary.
The lipoprotein lipase, or LPL, will come out
of a cell that made it and become
embedded in the capillary endothelial
cell. That LPL will then take
chylomicrons and digest their fats into
glycerol and fatty acids. The chylomicron
gets digested into a chylomicron remnant
and that chylomicron remnant
gets taken up by the liver.
Meanwhile the glycerol and fatty acids
are available to the tissue that
made the LPL because the job of this
capillary is to feed that tissue.
So those nutrients get digested in the
capillary and infused into the cell.
The expression of glucose transporters and
LPL is very different. If you look at
glucose transporters, all tissues in the
entire body express GLUT1 and GLUT3.
These glucose transporters are high
affinity for glucose and not dependent
on insulin. That gives all tissues access
to the glucose that they need under any
condition. The liver and pancreatic
beta-cells also make GLUT2. GLUT2 has
low affinity, meaning it's only activated
at high concentrations of glucose and
it's not dependent on insulin. That
allows the liver and the pancreas to
ramp up glucose uptake when blood
glucose concentrations rise beyond their
normal level. In addition, muscle, heart
and adipose tissue make GLUT4.
GLUT4 has moderate affinity and it's
increased by insulin and AMPK.
AMPK increases GLUT4 because the cell
needs more energy.
Insulin increases GLUT4 because
the body needs the cell to take up
energy or to take up specifically glucose.
So we have all tissues expressing
GLUTs, some more than others,
some extra GLUTs that play specific
functions such as a response to insulin,
response to energy status or response to
circulating glucose. If you look at the
expression of LPL, it's expressed much
more limitedly. Almost all of the LPL is
expressed in muscle, heart and adipose
tissue. We know most about the LPL that's
expressed in those tissues. What we know
is that high energy status shifts
expression away from muscle and heart
and toward adipose. By contrast
low energy status does the opposite.
So think of the fat traveling through the meal,
remember it goes to the heart first.
If it goes to the heart first then if energy
status is low and the heart really needs
fat, the heart gets first access to that
fat and takes it up. But if energy status
is high the heart just looks at the fat and
it's like, "No I don't want this," that leaves
more available to muscle and adipose
tissue, but muscle also looks at that fat
and says "No, I don't want this." By contrast adipose LPL
is high under conditions of high energy
status. That makes fat go to adipose
tissue under conditions of high energy
status. Meanwhile there is also LPL
expression in macrophages, lung, kidney,
brain and lactating mammary glands.
The expression is much smaller than in
muscle, heart and adipose tissue; the
the regulatory mechanisms are
diverse and poorly understood. A typical
review of LPL expression across tissues
won't even mention its expression in the
pancreas, but if the pancreas doesn't
make LPL, how is it supposed to take up
postprandial fat from chylomicrons?
If you know studies that look at human
beta-cell LPL, please send them to me.
I couldn't find any, but I found studies in
mice. And what these studies show is that
in mice pancreatic beta-cells do make LPL.
However, under almost any condition the LPL is
inside the beta-cell. If the LPL is
inside the beta-cell that means there's
no LPL in the capillary lumen. That means
there's no LPL to digest chylomicrons.
That means that LPL does nothing to get
fat into that beta-cell. They've taken
the mice and they've subjected them to
fasting, to refeeding, to a normal chow diet,
to a high-fat diet, and the LPL just
sits in the pancreatic beta-cell.
The only conditions that make it leave the
beta-cell and go into the capillary
lumen, in these mouse and mouse cell
experiments, is high glucose
concentrations. We're talking 20 millimolar,
conditions of untreated diabetic
concentrations of high glucose.
That means that only under conditions of
very high glucose would you ever get fat
going into the pancreatic beta-cell
through locally expressed LPL.
But there's another way that fat in the
postprandial state could reach the
pancreatic beta-cell and that's from
fatty acid spillover. Let's say you have
an LPL-producing tissue that puts LPL
into the local capillary bed; it digests
chylomicron triglycerides into free
fatty acids and glycerol. In general
these are completely or mostly taken up
by the LPL-expressing tissue. But what if
you have so much fat that you overwhelm
that tissue and there's no room to take
up all the fat that's been digested?
Or what if you're fat, what if that tissue
is fat, and all the room within that cell
is taken up by fat; or what if the energy
status of that cell is so high that it's
blocking the uptake of everything?
In those cases you may get digestion of the
chylomicrons into free fatty acids and
glycerol that get left in the blood.
And since they don't get taken up by the
tissue, they leave the capillaries through
the veins and then they eventually make
their way into the circulation to get to
other tissues such as the pancreas.
That's called fatty acid spillover, and it's
thought to be increased by
high-fat diets, obesity and insulin resistance.
So, so far we have glucose
going to the liver first and we're
repleting the hepatic glycogen. Whatever
glucose is left over, it goes to the heart
and eventually can make its way
to the pancreas.
By contrast fat goes through the
lymphatic system, it goes first to the heart
and if the energy status in the heart is
low the heart gets first dibs on the fat,
if it's high that fat preferentially
goes to adipose tissue, not necessarily
ever making it to the pancreas. Glucose
transporters are expressed in the
pancreas. In fact the pancreas also
expresses GLUT2, a special glucose
transporter that makes glucose uptake
kick in even higher than normal whenever
circulating concentrations of glucose are high.
The liver does the same thing.
That means that high blood glucose goes
preferentially first to the liver to
replete hepatic glycogen, and second to
the pancreas for insulin stimulation.
In addition, the pancreas also has a special
form of hexokinase that doesn't get
inhibited by glucose-6-phosphate.
We talked before about how if you don't go
through glycolysis, glucose 6-phosphate
builds up and that rejects the glucose.
In the pancreatic beta-cell we have
glucokinase, a special form of hexokinase
that is not inhibited by
glucose-6-phosphate. That means that the
pancreatic expression of glucose
transporters and hexokinase isoforms is
designed to facilitate glucose uptake
into the pancreas, not because the
pancreas needs more glucose, but
specifically because the circulating
glucose concentrations are high. This is
not true for fat because
the pancreatic beta-cell appears not to
move LPL into its local capillary bed
unless possibly exposed to very high
concentrations of glucose mimicking
untreated diabetes. But the pancreatic
beta-cell still gets some fatty acids in
the postprandial state from fatty acid
spillover if the meal is very high in
fat or if the person is obese or insulin
resistant. So it seems then that it is
the anatomy and the physiology that
coordinate the inter-organ distribution
of these nutrients that drives the
effect on insulin secretion instead of
the biochemistry and the molecular and
cellular biology that occurs within the
pancreatic beta-cell. Nevertheless the
mechanism that I showed you at the very
beginning is what's called "triggering."
There's also an amplification step to
insulin secretion, and the amplification step
is much more complex and much more
controversial. So let's say that it's
glucose that is primarily the nutrient
that can raise ATP levels in the
pancreas, inhibiting the potassium
channels, depolarizing the membrane,
activating the calcium channels, getting
a rise of intracellular calcium,
initiating a cascade of events that
leads insulin to be secreted.
Well there's that and that's the
uncontroversial consensus part of this.
But the amplification step can make the
cell more sensitive to the influx of
calcium or can increase the capacity to
respond to that calcium by making more
insulin ready to be mobilized. And these
amplification signals are, number 1,
very complex, and, number 2, not at all
agreed upon. We may be moving toward a
consensus eventually, but if you look at
even recent reviews of this topic you'll
see lots of controversy about which
mechanisms are more important,
and even some controversy over which
mechanisms actually play out in the live
human at all. If we look at these
amplification signals what we will see
is that anaplerosis, which is the
filling up of citric acid cycle
intermediates, can occur in a way that
overfills the citric acid cycle and leads
to cataplerosis, which is the leaving of
citric acid cycle metabolites including
their transport into the cytosol. Since
anaplerosis is primarily the domain of
carbohydrate and as a secondary source
protein rather than fat, then that means
that cataplerosis is primarily enabled
by carbohydrate and secondarily protein.
That cataplerosis then leads to
amplification signals. Lipogenesis leads
to various downstream processes from the
accumulation of fat in the cell. Lipogenesis
is driven by malonyl CoA.
Malonyl CoA can be derived from
anything that makes acetyl CoA and
citrate because citrate activates the
conversion of acetyl CoA to malonyl CoA,
as we talked about in the
lesson on fat burning. Since carbs,
protein, and fat can all generate acetyl CoA,
and can all generate citrate, and carbs, protein,
and fat can all lead to malonyl Coa and
lipogenesis and can all, to some extent,
lead to that amplification symbol.
That amplification signal.
Some of this is driven by the
pentose phosphate pathway's production
of NADPH, a topic that we haven't covered yet.
It's carbs specifically that support
the pentose phosphate pathway and
provide that NADPH that go into that
amplification signal. So what we see
then is that all of the macronutrients
can make some contribution to
amplification. But carbohydrates are the
most versatile out of all of them and
fats are the least versatile.
Perhaps that versatility in providing
the amplification signal is simply a way
to gauge the versatility of
carbohydrate. Because carbohydrate is
also the most versatile in supporting
the biochemical pathways that you
actually need. So if the body is trying
to judge whether it has enough energy, it
makes sense that part of that signal
would be specifically driven by
carbohydrate because carbohydrate is the
thing that supports the pentose
phosphate pathway, whereas fat doesn't.
Carbohydrate is the thing that supports
anaplerosis of the citric acid cycle,
which fat doesn't to anywhere
near the same extent. And so it
may actually be that the pancreatic
beta-cell is, as the mechanism of
triggering would suggest, simply gauging
energy status. And it may be that the
pancreas correctly looks at carbohydrate
as especially valuable source of energy
because the energetic uses of
carbohydrate are more versatile than
those of other macronutrients,
especially fat. And if carbs provide
energy plus the specific uses of energy
that fat can't, then carbs are a uniquely
valuable source of energy. So when I look
at this what I see is the pancreatic
beta-cell wants to make sure that we
have enough energy; but it wants to
specifically make sure that we have
enough glucose because of the specific
things we can do with that energy that
are much harder to do with the energy we
derive from fat. So is insulin responding
to carbohydrate specifically or is it
responding to energy status in general?
The answer is both.
The anatomy and physiology bias
carbohydrate to the pancreas when
it reaches high concentration providing
the liver has the first opportunity
to replete the hepatic glycogen pool.
That same anatomy and physiology biases
fat toward the heart and muscle under
low-energy conditions and toward adipose
tissue under high-energy conditions, and
biases it away from the pancreas under
any conditions except possibly severe
hyperglycemia.
Then the biochemical pathways
within the pancreatic beta-cell
are mostly responding to cellular energy
status. But because the pancreatic
beta-cell's energy status is best
nourished by carbohydrate, then
carbohydrate plays a specific role in
triggering insulin. Carbohydrate also
plays the dominant role, with protein second
and fat a distant third in amplifying
that insulin signal. Because, perhaps, the
pancreas cares that we don't just have
enough total energy, but that we have the
versatility that we get from having
carbohydrate as a part of that energy.
The audio of this lesson was generously
enhanced and post-processed by
Bob Davodian of Taurean Mixing, giving
you strong sound and dependable quality.
You can find more of his work at
taureanonlinemixing.com.
To continue watching these lessons, you
can find them on my YouTube channel at
youtube.com/chrismasterjohn.
Or on my Facebook page at
facebook.com/chrismasterjohn.
Or you can sign up for MWM Pro, to get
early access to content, enhanced keyword
searching, self-pacing tools,
downloadable audio and transcripts,
a rich array of hyperlinked further
reading suggestions, and a community
forum for each lesson. If you really
want to own these lessons, study them
and get the most out of them, you can
sign up for MWM Pro at
chrismasterjohnphd.com/pro.
Signing off, this is Chris Masterjohn of
chrismasterjohnphd.com.
You've been watching
Masterclass with Masterjohn.
And I will see you in the next lesson.
-------------------------------------------
ANNE BANCROFT IN TO BE OR NOT TO BE - Duration: 0:14.
For more infomation >> ANNE BANCROFT IN TO BE OR NOT TO BE - Duration: 0:14. -------------------------------------------
Superman or Batman - Which Kind of Leader Are You? | TIAnimate - Duration: 2:38.
Before defining your leadership style,
you need to find out which type of leader are you:
Superman or Batman?
If you are a Superman-typed leader,
you might realize that
you are a naturally-born leader.
You might have leadership traits such as confidence, charisma,
intelligence, and some other traits.
But it does not mean that Superman
would just become a great leader from that.
Nonetheless, Superman needs to know himself first
so that he could find certain values that he believes in.
Just like when he believed he could fly,
then he actually did.
Unlike Superman, Batman does not have those advantages
since he was born.
Batman, a.k.a Bruce Wayne
was just a normal human being without possessing superpower.
So, if you're a Batman leader,
you need to understand your competitors
and their strengths over you
to excel Superman Leaders.
Although Superman has extraordinary talents,
he never settles down with his achievements.
If you're a Superman leader,
you need to follow his example.
Because you'll never know how far you can go
if you don't keep exploring your talents.
On the other hand, Batman has limitations.
So if you're a Batman leader
remember that your limitations
are not your barriers for success.
In contrast, these limitations can motivate you
to think creatively and continue to innovate
and to solve various problems.
Just like Batman who utilizes his belt,
you can also use technology to help you.
But keep in mind: use it only when it's needed.
Despite their differences, both Superman and Batman leaders
have the same opportunities to be great leaders.
As long as you're resilient and you don't see failure as a defeat,
your chance to becoming a great leader is widely opened.
-------------------------------------------
5 Home Remedies To Get Rid Of Slipped Or Herniated Disc - Duration: 3:07.
In this video you will learn about 5 Home Remedies To Get Rid Of Slipped Or Herniated
Disc.
The vertebrae are the backbone of the body.
Any problems in our spine can lead to problems in your daily movement and activities.
Our spinal cord is made up of small bones known as vertebrae that are attached to each
other.
These bones are lined by discs which protect them from shock.
These discs have gel-like inner portion and a strong outer portion.
Any kind of injury or damage to the discs can cause the inner portion to come out and
cause a bulge like appearance on the outer part.
This disorder is known as herniated disc or a slipped disc.
The herniated disc can affect any region of your spine but the lower part is more at risk
due to continuous bending and turnings.
The symptoms of herniated disc or slipped disc are: 1.
Pain and numbness which usually occurs on any one side of your body; 2.
Pain that moves up to arms or moves down to the legs; 3.
Tingling or a burning sensation in the region of the slipped disc.
The 5 Home Remedies to Get Rid of Slipped or Herniated Disc are:
1.
Heat or Cold Therapy You can use both hot and cold water bags on
the area where you feel the maximum pain.
Do the alterations between cold and hot water.
However, remember to keep at least half an hour gap between both of them.
2.
Physiotherapy and Yoga Physiotherapy is all about proper exercises
and stretches which will improve the disc shape to a great extent.
Physiotherapy helps in promoting faster healing of this disorder.
Doing some yoga poses also helps in healing herniated disc or slipped disc.
3.
Use Turmeric Turmeric contains curcumin which is a very
good anti-oxidant and anti-inflammatory agent.
Turmeric helps in reducing the pain because of slowed blood circulation to the area of
pain.
4.
Acupressure and Acupuncture It is an excellent pain management method.
The pressure is used for relieving the pain from the swelled area.
In acupressure fingers are used and in acupuncture needles are used.
5.
Take bath with Epsom Salt Epsom salt is widely used as a natural painkiller
and anti-inflammatory agent.
Add 3 to 4 cups of salt in a hot water bath.
Stay inside the bath for at least 15 minutes.
Doing this will help you to achieve maximum relaxation.
Note: Do not use this remedy if you are diabetic or pregnant.
So what are you waiting for, start taking these home remedies and consult a doctor whenever
you feel any kind of severe pain.
Thanks for watching this video, if you enjoyed this video, please do not forget to like and
subscribe to our channel.
In this channel you will get information about various health related topics.
Wishing you good health in your life, bye.
-------------------------------------------
how to install minecraft on you pc or mac tutorial - Duration: 5:51.
i hope you luv this video subscribe and leave a like and even tell your friends about it!!!! "if they want to know how but don't definitely tell them :)"
-------------------------------------------
Humanity does not need sex, color or religion - Duration: 11:36.
For more infomation >> Humanity does not need sex, color or religion - Duration: 11:36. -------------------------------------------
UV Air Purifier - Home Or Business UV Air Purifier - Duration: 1:16.
Are you looking for Air Oasis UV Air Purifier?
Are you concerned about the air quality in your home or business or need allergy or asthma
relief?
Then you need our Air Oasis UV air purifier sanitizer.
Air Oasis UV isn't a filtration air cleaner but an air and surface sanitizer.
Unlike inefficient noisy HEPA cleaners that capture pollutants, the Air Oasis UV Air Purifier
uses ultraviolet light in conjunction with photocatalytic oxidation which sends out powerful
oxidizing cleaning agents eliminating odors, VOCs, mold, viruses and bacteria in the air
and on surfaces.
Air Oasis UV sanitizers have unmatched test data.
Air Oasis has the Mobile personal travel sanitizer, the 1000 and 3000 models for home or office,
and commercial models.
AirOasisUV.com has sold commercial models to food stores, kennels, vet clinics, doctors'
offices, hospitals, salons, churches, schools, NFL and MBL lockers rooms and many more.
For discounts on Air Oasis UV air purifier sanitizers, visit AirOasisUV.com or give us
a call toll free 855-488-8806.
-------------------------------------------
A Street or a Zoo : Learn Hindi with subtitles - Story for Children "BookBox.Com" - Duration: 2:55.
For more infomation >> A Street or a Zoo : Learn Hindi with subtitles - Story for Children "BookBox.Com" - Duration: 2:55. -------------------------------------------
[ [ MMD SHORT ] ] Why Bad Boy or Blue Can't Get Girls [Motion by Monica x Isabel] +Captions - Duration: 0:59.
But I told her!
That she's cute! That I love her!
Exactly, she probably thought it was a prank.
I mean, you do seem superficial (and gay).
Bad Boy: WHAT DID YOU JUST CALL ME IN DAT THERE PARENTHESIS >:d
I'll have you know I graduated top of my class in the Navy Seals, and I've been involved in numerous secret raids on Al-Quaeda, and I have over 300 confirmed kills. I am trained in gorilla warfare--
The FitnessGram™ Pacer Test is a multistage aerobic capacity test that progressively gets more difficult as it continues. The 20 meter pacer test will begin in 30 seconds. Line up at the start. The running speed starts slowly, but gets faster each minute after you hear this signal-
It's better than you who never says anything.
w0t u say m8
You couldn't even say hey to Neru or tell her that she's kawaii desuuuuuu.
I told you, it's not like that (it's because I'm gay.)
If you keep acting like this, you're going to miss your chance.
*triggered fist*
I TOLD YOU, I'M GAY--- I MEAN IT'S NOT LIKE THAT, YOU SUPERFICIAL BAKA D:<!!!!
W0T M8?!!!!!! I CAN'T HEAR YOUUUUUUUUUUUUU!!
YOU ARE A NASTY BOY ( ͡° ͜ʖ ͡°)
YOU ARE CLOSET PERVERT (and gay).
*constipation noises*
( ͡° ͜ʖ ͡°)( ͡° ͜ʖ ͡°)( ͡° ͜ʖ ͡°)
Bad Boy: STOP TOUCHING MY BUTT
Blue: Kay. ( ͡° ͜ʖ ͡°)
SHASH YA'LL MOUTHS
...
( ͡° ͜ʖ ͡°) wow
[distant fujoshi screaming]
(me after watching boku no pico)
Bad Gir--
MOMMY RAC!!! BAD BOY BROTHER IS CHEATING aGAIN!!! SAVE US ALL!! I WANT LIGHTNINGBOY!!!
-------------------------------------------
Which Rice Has Less Arsenic: Black, Brown, Red, White or Wild? - Duration: 5:15.
For more infomation >> Which Rice Has Less Arsenic: Black, Brown, Red, White or Wild? - Duration: 5:15. -------------------------------------------
No Degree: Apply For Job Or Internship? - Duration: 8:09.
Hey, what's up?
John Sonmez here from simpleprogrammer.com.
Tired of pushy recruiters sending you LinkedIn requests for jobs you have no interest in?
Tired of blasting out resumes into the dark?
If so, you should check out Hired.com.
Hired.com flips job searching on its head by having top employers like Facebook come
to you after you fill out one simple application.
You also get your own job coach to help you on your next job search.
If you haven't checked it out, I highly recommend you at least fill out the application.
Just go to Hired.com/simpleprogrammer.
When you get hired with Hired, you'll get double the normal sign-on bonus for using
that link.
I got a question from—oh, and he gave me the pronunciation.
He's from Bulgaria.
He says Lyubomir.
At least I think that's Lyubomir.
Lyubomir says, "I can either go to the US to work for 14-16 hours a day for $10 an hour
(That's a lot of money in Bulgaria) or get an internship doing some programming for little
or no pay.
What should I do the 4 months in summer when I don't have college?"
He says he's from Bulgaria finishing up his second semester studying Computer Science
and Information Systems.
His college is extremely expensive, $5000 a year with a 60% scholarship.
For Bulgaria, that's expensive.
He's been doing freelance web development on the side for pretty lucrative amounts of
money, but it's not enough to pay for his education.
He'd either have to go to the US and work two jobs in the summer or have a large student
loan that I have to pay off after I graduate.
If I understand the question correctly, I think what he's saying is that he's either
going to go to the US and work 14-16 hours a day at about 10 bucks an hour or do an internship
doing some programming with no or little pay in Bulgaria.
What should you do in this case?
I would highly recommend—you know, I talked about this before in a video.
I think someone asked in a video about going to the US or staying in their country and
I had recommended going to the US.
If we can find that video, I don't remember the name of it, but I would highly recommend
going to the US and doing the 10-14-hour days for 10 bucks an hour just because of the connections
that you're going to make there, especially working at a company being paid in the US,
and the perspective change that you're going to have.
I mean I have my own world view and my own perspective, but I've seen on the flip side.
I went to China.
You can check out my videos in China and I've gone to a lot of third world kind of countries
or places where the cost of living is much less, where people make a lot less and they
live in a lot worse conditions.
I realized how plentiful the US is and how much opportunity there is here and how fortunate
I am to be here and to have that opportunity.
It's sort of made my perspective bigger to understand that opportunity that I maybe was
taking for granted.
I think, again, I haven't done this, but I think the other perspective is also valuable.
I think if you're from somewhere like Bulgaria and you come to the US and you see—I mean
I've actually had the other experience.
I'll talk about it in a second, but, essentially, I think if you come to US and you see how
much everyone's got—is making so much money and there's so many expensive stores, and
all of this stuff and how much things cost, it may motivate you and make you realize that
there is—because you're working in this global economy.
Maybe you're underpricing yourself.
Maybe you're undervaluing yourself because you're used to what is expensive or what is
the current value in Bulgaria, which is a lot less.
Seeing something more grand and more extravagant and of a higher level can make you want to—not
only want to reach that level, but it can make you realize that it's possible and that
there's—for a lot of people, it's the norm.
Now, again, there's opportunities and there's all of these things, but as we're moving to
more of a global economy especially for programmers, there is—a lot of it is perception.
A lot of it comes down to perception and I'll tell you like I've had this experience when
I've gone to places like Manhattan and gone to 5th Street in Manhattan.
You might think that you're doing pretty well, but you go to 5th Street in Manhattan and
you're like, "Man, I am poor."
Or you go to Vegas to some of these places in Vegas where—I went to this one restaurant
and they had this Japanese kobe beef.
Do you know how much that beef costs—like 4 ounces of beef?
I'm embarrassed to tell you how much it cost me, but it cost me like 200 bucks, something
like that.
It was like 150 or 200 bucks.
Somewhere around that range for like 4 ounces of beef.
Now, I wouldn't do that all the time.
Obviously, I'm not that rich but I wanted to try it once, and there are people that
do, that lived that way.
It expanded my mindset to say, "Wow.
This is interesting.
For some people, this is just a norm.
Why do I have such a limited mindset that I don't think this is the norm?"
I'm not saying that money is everything and that—you know, all this but I'm just saying
that sometimes seeing how the extravagant or seeing how the wealthy live can make you
realize that that could be your like—it could adjust you to that where it could set
your sights a little higher because a lot of times we set our sights too high or—I
mean too low.
We should set them a little bit higher.
I know this is kind of a weird way to go from your question, but, honestly, I would come
over to the US and take that opportunity and just—I feel like it will expand your perspective.
It will give you lot of opportunities in the future in the US versus doing an unpaid internship
in Bulgaria.
I think that it's going to carry more weight.
Plus, the other thing to think about too is that if you do try to get a job in the US
or you try to do freelancing, if you have US clients on your resume and on your portfolio,
that's going to make a bigger difference.
If it's all Bulgarian clients and you try to get a job somewhere else or you try to
court a US client, it's going to be harder because they're going to say, "Well, I don't
know like is this legit?
Does this measure up?"
They're going to have these perceptions and—if you're like, "Oh, I interned at IBM in the
US for four months," that's going to look much better for you.
Again, I don't know about this.
I don't have your perspective so I can't tell you 100%, but I would say that just for
my own experience and what I've seen and all the people that I know that—I know a ton
of developers that came over here from India.
There's one in particular that the dude started following my channel, I think like three or
four years ago and started reading my stuff and my blog, and he was making like nothing
in India like very little, and he came to US and he's making like almost $200,000 a
year in the US now.
I mean can you imagine that?
A lot of it was the mindset shift.
A lot of it was because—when I've talked to him, he said that a lot of watching my
videos and just realizing what was possible made him want that and set his bar that high,
and then all of a sudden he's—I mean it's unbelievable where he's been and there's couple
of stories like that.
I mean you've seen the one on my channel where i told about the story, the guy that emailed
me that—also from India—That end up being extremely successful.
I can't remember the—Skip MBA.
That's his name.
All right.
That's all I got for you.
Good luck.
If you have a question to email me, email me at john@simpleprogrammer.com.
Make sure that you click that Subscribe button if you haven't already and click the bell
to make sure you don't miss any videos when they come out.
I'll talk to next time.
Take care.
-------------------------------------------
Overly Excited Tourist Loses It At San Diego Comic-Con - Duration: 2:29.
- Surf's up, honey.
I'm in sunny San Diego.
They're havin' some sort of a costume party or somethin'.
Let's go find us a cot-stume, and have a good time.
(seagulls cawing)
(fireworks exploding)
Yeah, buddy, that's the one.
Yeah, yeah, yeah, yeah, yeah, yeah, yeah, yeah.
Whoa baby boy,
I got my cat-stume, and I am ready to go.
I am Batman.
Hasta la vista, buddy.
Hey, Alexa, where are the restrooms at this costume party?
Alexa!
50 years of Penis in Japan.
Only in Santiago.
Scoogy boogy boo, how are you?
Are you joking my ass?
They got a life size Shrek.
Donkey.
One thing I'll say about Sandy Bagels
is they have a whole lot of danosaurs.
Look at these nasty bad skulls.
I'm spooked as heck.
♫ Transformers,
♫ Robots in-they are cars.
Shrek!
I'm an ogre.
Toly Crobus!
They got a life size Colin O'Brien.
Hi, honey.
- Psychosis.
- Are you jokin' my ass?
Get in my ass and think about what you've done.
Look at the size of this pineapple.
They say it's a 100 feet bit, and...
I am gay.
Wake up, silly ass, we're having a costume party.
Uh-oh, Batman and Brain,
we better not fight.
- I'm gonna break your back, Batman.
- Oh, Jesus Christ!
Toly Crobus!
They got a Lego...
Super...
man.
I'll smash his ass for a hundred bucks.
Holy snopes, they got a real live Henry Simpson
holding a...
a...
a ball.
Jumpin' Jefferson,
it's pro wrestler Sting!
Hi, boy!
Ew, icky bad, look at all these nasty poops.
Shrek!
Donkey,
I'm an ogre, Donkey.
I love Stan Liego!
Ass full o' nuts, what a day I've had
here at this impromptu Halloween party.
Everyone was pretty ugly,
but it was still a pretty good time.
I think it even was the best day of my whole life.
(upbeat techno music)
-------------------------------------------
PROTECTIVE MOM! Kajol Will Be Angry If Yug Or Nysa Gets Papped Like Suhana Khan For Pictures - Duration: 1:45.
PROTECTIVE MOM! Kajol Will Be Angry If Yug Or Nysa Gets Papped Like Suhana Khan For Pictures
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