GIT Module for Undergraduates

1. Dr Zahid Azeem
AJK Medical College, Muzaffarabad
EMR Module;
MBBS Class 2020

2. Overview
Four major organs play a dominant role in the fuel
metabolism:
1- Liver
2- Adipose
3- Muscle
4- And brain.
These tissues contain unique sets of enzymes such that
each organ is specialized for the storage, use and
generation of specific fuel.

3. Fine Coordination in these four
organs

4. Integration of Energy Metabolism:
The integration of energy metabolism is controlled
primarily by;
1- Insulin
2- Glucagon
However, supporting role by
3- Epinephrine and norepinephrine (catecholamines)

5. Insulin
Insulin is a polypeptide hormone produced by the beta-
cells of islets of langerhans_ clusters of cells that are
embedded in the exocrine portion of the pancreas.
Islets of Langerhans: 1-2% of the total cells of pancreas.
-Coordinates use of fuels by tissues
-anabolic metabolically; synthesis of glycogen
-triacylglycerols -protein

7. Insulin Chemistry and Synthesis
Insulin is a small protein; - has a molecular weight of
5808da. It is composed of two polypeptide chains
(50 amino acid) connected to each other by
disulfide linkages
Beta cells - beginning with translation of the insulin
RNA by ribosomes attached to the ER to form an
insulin preprohormone (11500 da) - cleaved in the
ER to form a proinsulin (9000 da) - further cleaved
in the Golgi apparatus to form insulin - secretory
granules

8. C – peptide (Connecting Peptide) has no biological activity, but its
estimation in plasma serves as an useful index for the endogenous
production of insulin.

9. Porcine and bovine Insulin

10. Production of Human Insulin by genetic Engineering

11. Insulin Storage
Insulin stored in the cytosol in granules that, given
the proper stimulus, are released by exocytosis.
it has a plasma half-life that averages only about 6
minutes - degraded by the enzyme insulinase
mainly in the liver, to a lesser extent in the kidneys
and muscles
This short duration of action permits rapid changes in
circulating levels of the hormone.

16. Gastrointestinal Hormone
Most gastrointestinal hormones favor insulin release.
1- Cholecystokinin
2- Gastric inhibitory polypeptide
Both are referred to as “incretins’’

17. Inhibtion of insulin
The synthesis and release of insulin are decreased when
there is a decrease of dietary fuels and also during
stress
(fever or infection).
Epinephrine mediates these effects in response to
stress, trauma and extreme exercise.
Epinephrine release is controlled by CNS; it will rapidly
mobilize energy fuels e.g, glucose, FFA,.

18. So, SNS (sympathetic nervous systm) will replaces
plasma glucose concentration as controlling influence
over B-CELL SECRETION.

19. Mechanism of Insulin Action
Insulin binds to its specific receptors
1- Liver
2- Muscle
3- Adipose

20. Insulin first binds with and activates a membrane receptor
protein (300,000)
The insulin receptor is a combination of four subunits held
together by disulfide linkages:
Two alpha subunits that lie entirely outside the cell
membrane
Two beta subunits that penetrate through the membrane,
protruding into the cell cytoplasm

21. Insulin binds with alpha
↓
beta unit autophosphorylated
↓
tyrosine kinase
↓
phosphorylation of multiple other intracellular enzymes
including a group called
insulin-receptor substrates (IRS)

24. Membrane effects of Insulin
Glucose transport in some tissues such as skeletal
muscles nd adipocytes increase in the presence of
insulin. Insulin promotes the recruitment of Insulin
sensitive glucose transporter (GLUT-4) from a pool
located in intracellular vesicles.
- There are some tissues in our body have insulin-
independent system for glucose transport.
- Hepatocytes, erythrocytes and brain cell, renal tubule
and cornea.