INSULIN

Overview

Four major organs

play a dominant role

in fuel metabolism.

Integration of energy

metabolism is controlled

primarily by the actions

of

insulin and glucagon.

Polypeptide hormone produce by the beta cells of the islet of Langerhans of the pancreas.

Most important hormone coordinating the use of fuels by tissues.

Metabolic effects-anabolic

Favoring the synthesis of

glycogen, triacylglycerols

51 amino acids.

Polypeptide A and B,

linked together by

disulfide bonds.

Intramolecular

disulfide bridge

between amino acid

residues of the A

chain.

Synthesis of insulin

2 inactive precursors cleave to form active

hormone and C – peptide. C – peptide is

essential for proper insulin folding.

Stimulation of insulin secretion

Insulin and glucagon

secretion is closely

coordinated at the

islet of Langerhans.

Secretion is regulated

so that the rate of

hepatic glucose

production is kept

equal to the use of

glucose by peripheral

tissues.

Stimulation of Insulin secretion is increased

by Glucose.

ß cells contain Glut-2

transporters and have

glucokinase activity and

thus can phosphorylate

glucose in amounts

proportional to itsactual

concentration in blood.

Ingestion of CHO rich

meal leads to a rise in

blood glucose, which is

a signal for insulin

secretion and decrease

glucagon synthesis and

release.

Stimulation of Insulin secretion is stimulated

by Amino Acid

Ingestion of protein

causes a transient rise

in plasma amino acids

level, which in turn

induces the secretion of

insulin.

Elevated plasma

arginine stimulates

insulin secretion.

Stimulation of Insulin secretion increased by

Gastro- Intestinal hormones.

Cholecytoskinin and gastric-inhibitory peptide increased insulin secretion.

Released from SI in response to oral glucose and cause anticipatory rise in insulin levels.

This may account for the fact that the same amount of glucose given orally induces a much greater secretion of insulin that is given

Inhibition of insulin secretion: Epinephrine.

Scarcity of dietary fuels and during the period of stress,

Direct effect on energy metabolism

causing glycogenolysisand

Gluconeogenesis,

Can override the normal glucose-

stimulated release of insulin,

In emergency situation, the sympathetic nervous system largely replaces the plasma glucose concentration as the controlling influence over ß cells Secretion.

Metabolic effects of insulin : Carbohydrate

metabolism.

Promotes storage in 3 tissues--

In liver & muscle, increase glycogen synthesis.

In muscle and adipose,increaseglucose uptake by more GLUT-4.

Insulin decreased the production of glucose by inhibiting glycogenolysis and gluconeogenesis.

GLUT – 4 Transport protein

Metabolic effects of insulin- lipid

metabolism

Decrease TAG

degradation.

Insulin inhibits hormone

sensitive lipase ,

Increaes TAG

synthesis.

Insulin increases

transport and

metabolism of glucose

into adipocytes

providing substrate for

glycerol -3- phosphate

for TAG synthesis.

Also increases the

lipoprotein lipase,thus

providing fatty acids for

Metabolic effects of insulin : Protein

synthesis.

Insulin stimulates the entry of amino acids into

cells, and protein synthesis through activation of

factors required for translation.

Membrane effects of Insulin.

Receptor regulation

Binding of insulin is

followed by

internalization of the

hormone-receptor

complex.

Once inside the cell, the

insulin is degraded in

the lysosomes.

The receptors may be

degraded but most are

recycled to the cell

surface,

Characteristics of glucose transport in

various tissues,

Diabetes Mellitus

Type I

Insulin dependent

Juvenile onset

Causes--

-Increased blood glucose (300-1,200 mg/100ml)

-Increased blood fatty acids and cholesterol

-Protein depletion

Treated with insulin injections

Increases risk of heart disease and stroke

Can cause acidosis and coma

Type II

Non-insulin dependent.

Results from insulin insensitivity.

Elevated insulin levels.

Associated with obesity.

Can lead to insulin dependent form.

Treated with weight loss, diet restriction, exercise

and drugs.

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