2. 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.
3. 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
4. 51 amino acids.
Polypeptide A and B,
linked together by
disulfide bonds.
Intramolecular
disulfide bridge
between amino acid
residues of the A
chain.
5. Synthesis of insulin
2 inactive precursors cleave to form active
hormone and C – peptide. C – peptide is
essential for proper insulin folding.
6.
7. 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.
8. 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.
9. 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.
10. 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
11. Inhibition of insulin secretion: Epinephrine.
Scarcity of dietary fuels
and during the period of
stress,
Direct effect on energy
metabolism
causing glycogenolysis
and
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.
12. Metabolic effects of insulin : Carbohydrate
metabolism.
Promotes storage in 3
tissues--
In liver & muscle,
increase glycogen
synthesis.
In muscle and
adipose,increase
glucose uptake by more
GLUT-4.
Insulin decreased the
production of glucose
by inhibiting
glycogenolysis and
gluconeogenesis.
14. 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
15. 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.
17. 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,
21. 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
22.
23. 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.