Essay About Physiologic Effects Of Insulin And Insulin Receptor

Physiologic Effects of Insulin
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Stand on a streetcorner and ask people if they know what insulin is, and many will reply, “Doesnt
it have something to do with blood sugar?” Indeed, that is correct, but such a response is a bit like
saying “Mozart? Wasnt he some kind of a musician?”
Insulin is a key player in the control of intermediary metabolism. It has profound effects
on both carbohydrate and lipid metabolism, and significant influences on protein and
mineral metabolism. Consequently, derangements in insulin signalling have widespread and
devastating effects on many organs and tissues.
The Insulin Receptor and Mechanism of Action
Like the receptors for other protein hormones, the receptor for insulin is embedded in the plasma
membrane. The insulin receptor is composed of two alpha subunits and two beta
subunits linked by disulfide bonds. The alpha chains are entirely extracellular and house
insulin binding domains, while the linked beta chains penetrate through the plasma membrane.
The insulin receptor is a tyrosine kinase. In other
words, it functions as an enzyme that transfers
phosphate groups from ATP to tyrosine residues on
intracellular target proteins. Binding of insulin to the
alpha subunits causes the beta subunits to phosphorylate
themselves (autophosphorylation), thus activating the
catalytic activity of the receptor. The activated receptor
then phosphorylates a number of intracellular proteins,
which in turn alters their activity, thereby generating a
biological response.
Several intracellular proteins have been identified as
phosphorylation substrates for the insulin receptor, the best-studied of which is insulin
receptor substrate 1 or IRS-1. When IRS-1 is activated by phosphorylation, a lot of things
happen. Among other things, IRS-1 serves as a type of docking center for recruitment and
activation of other enzymes that ultimately mediate insulins effects. A more detailed look at
these processes is presented in the section on Insulin Signal Transduction.
Insulin and Carbohydrate Metabolism
Glucose is liberated from dietary carbohydrate such as starch or sucrose by hydrolysis within the
small intestine, and is then absorbed into the blood. Elevated concentrations of glucose in
blood stimulate release of insulin, and insulin acts on cells throughout
the body to
stimulate uptake, utilization and storage of glucose. The effects of insulin on glucose
metabolism vary depending on the target tissue. Two important effects are:
Insulin facilitates entry of glucose into muscle, adipose and several other tissues.
The only mechanism by which cells can take up glucose is by facilitated diffusion through
a family of hexose transporters. In many tissues – muscle being a prime example – the
major transporter used for uptake of glucose (called GLUT4) is made available in the
plasma membrane through the action of insulin.