00:01
Mechanism action of insulin, it will bond
to glucose transporters or the receptor.
00:07
When the receptor is bound to, there is something
called autophosphorylation, which is important
for you to know, intercellular beta subunit
receptors and please note that it works from
tyrosine kinase.
00:19
When you have tyrosine kinase, this then represents
your phosphorylation, phosphorylation.
00:26
Now, every once in a while, they will ask
about type 2 diabetes.
00:32
Think about type 2 diabetes, where is my problem?
Sure, it could be decreased insulin, but really
the problem could be at the level of the receptor,
take a look at the picture here.
00:45
You see the phospholipid bilayer, you have
a membrane, the spiraling blue ribbons that
you see there, those are the receptors.
00:53
It is then bound to two beta subunits, then
you have the autophosphorylation.
00:57
My point is this.
00:59
The receptors might be resistant to insulin
which are the round green circles.
01:05
If the receptors to insulin are then insensitive
or provide resistance, where is all my glucose?
It is not being taken up by the cell, it remains
back in my circulation, welcome to hyperglycemia,
welcome to diabetes mellitus.
01:21
What was that signaling pathway through your
receptor?
Tyrosine kinase.
01:27
Oh no, you don’t find receptor resistance
as being an answer choice.
01:34
Post receptor defect is a huge area of interest
in diabetes mellitus and when you say post
receptor defect, you are referring to the
fact that the signaling through tyrosine kinase
might not be taking place appropriately, type
2 diabetes mellitus.
01:51
Gene transcription can be up or down regulated
depending as to what the level of glucose
intake is.
01:57
In muscles and fat, glucose entry into the
cell through plasma membrane is enhanced by
these glucose transporters; glucose 4 transporters
are in fact insulin dependent.
02:13
Which ones are independent?
Glucose transporter 2.
02:18
4 are dependent, which in turn is regulated
by insulin.
02:24
Think of skeletal muscles, how many limbs
do you have, 1, 2, 3, 4, skeletal muscles;
glucose transporter 4, adipocytes, also sensitive
to insulin.
02:38
We will walk through more overall effect,
what kind, anabolic or catabolic?
Anabolic, anabolic, anabolic.
02:48
Insulin effect overall on your target.
02:50
There are three targets here, carbohydrates
we will walk through first.
02:55
In the liver, in the fat, in the muscle, it
is important that we pay attention to each.
03:00
In the liver, it is easy, decreased gluconeogenesis,
decreased glycogenolysis, increased glycolysis,
increased glycogenesis.
03:09
Insulin…
Insulin on fat, we have glucose uptake via
what kind of receptor?
Glucose transporter 4 and we have glycerol
synthesis.
03:22
What is the name of that lipase that you have
within your adipocyte?
Hormone sensitive lipase.
03:28
First, listen, lipase means what?
Breakdown, breakdown of lipid.
03:35
What do you know about insulin?
It is towards lipid.
03:39
So, what kind of effect does insulin have
on hormone sensitive lipase?
Inhibition, inhibition, inhibition.
03:47
What about muscles?
Anabolic, increased glucose uptake, increased
glycogenesis and glycolysis.
03:54
Now, before we move on, is there any such
pathway in your muscle that contributes to
gluconeogenesis?
Never.
04:06
In the muscle, there is never any gluconeogenesis,
right?
So, therefore, if it requires glucose, it
will break down glycogen.
04:14
Sure, you will have glycogenolysis, if it
requires glucose, or it will follow what’s
known as Cori cycle.
04:23
Keep that in mind, they love that from biochemistry
and physiology.
04:27
Let’s talk about fat, what is my topic?
Insulin.
04:31
What are you going to do with fat in insulin?
Build, build, build, build, therefore promotes
lipogenesis, inhibits lipolysis.
04:41
The fat, if you talk about lipid, adipocytes.
04:46
That glycerol that is being formed is then
being brought to the adipocyte in which it
is then being contributed or bound to your
3 fatty acids.
04:58
So, you are going to increase your fatty acid
and you have a glycerol, welcome to triglycerides,
tri means fatty acids, 3 of them, and glycerol
means what is being formed.
05:12
Collectively we will then have triglyceride
storage.
05:17
What about lipolysis in adipocytes?
Obviously inhibition, you inhibit this with?
Good, hormone sensitive lipase has been inhibited.
05:26
Fat metabolism.
05:27
Let’s talk about protein metabolism.
05:31
In the liver, it is going to decrease protein
breakdown; up in the muscle or in the muscle,
you are going to have muscle build, right,
anabolic, anabolic, anabolic.
05:40
So, we have increased amino acid uptake, increase,
increase protein synthesis.
05:44
A nice overview, biochemically, huh, of insulin,
so therefore, this sets us up beautifully
into what is going to happen with diabetes
mellitus.