Insulin: synthesis,sectretion,mechanism of action & degradation

1. INSULIN
DILSHANA FATHIMA
MSc. BIOCHEMISTRY

2. INTRODUCTION
 The endocrinal part of pancreas secretes various
types of hormones.
 These are produced by specialised tissue in the
pancreas called islets of langerhans.
 4 types of cells are recognised in theses islets
1. A cells(α cells) : produce glucagon
2. B cells(β cells) : produce insulin
3. D cells(δ cells) : produce somatostatin
4. F cells(PP cells) : produce pancreatic polypeptide

3. INSULIN
 Small polypeptide of mol.wt 5808
 Consists of 2 chains : A (21aā) & B (30aā)
 2 chains are connected to each other by disulfide
linkages
 An intrachain disulfide connects the 6th & 11th aā
within the A chain
 Interchain disulfide connects 7th aā of A & B chain
and b/w 20th aā of A & 19th aā of B chain
CHEMISTRY

4. SYNTHESIS
 Insulin is synthesised in the ẞ cells by usual cell machinery for protein synthesis
Initially preproinsulin is formed in the ribosomes
Cleaved in endoplasmic reticulum to form a proinsulin constiting of 3 chains
(A,B & C)
most proinsulin is further cleaved in golgi apparatus to form insulin composed of
A & B chain connected by disulfide linkages & the c chain peptide called
connecting peptide
Insulin & c peptide are packed in secretory granules & are secreted in equimolar
amounts
About 5-10% of final secreted product is still in the form of proinsulin

6. SECRETION
 The basic cellular mechanism for insulin
secretion by β cells is in response to increased
blood glucose concentration.

7. MECHANISM OF ACTION
 Insulin mediates its action through a plasma
memberane receptor which has a kinase activity.
 Insulin receptor consists of 2α & 2β subunits.
 α contain insulin binding site & β contain tyrosine
kinase domain.
 α & β held together by disulfide bonds.
 Both subunits are glycosylated in nature.
 α subunits are extracellular
 β is a transmembrane protein with globular domain at
extracellular & cytosolic surfaces

8.  Insulin binding to α subunit causes conformational
changes in the receptor complex which activates
autophosphorylation of β subunit.
 Once phosphorylated β subunit activates tyrosine
kinase which then phosphorylates multiple intracellula
proteins incliding insulin receptor substrate 1 (IRS 1)
 Phosphorylation of IRS 1 generate secondary signals
that couple the insulin pathway to transmembrane
glucose transport.

10. DEGRADATION
 Insulin is normally degraded within liver &
kidney, having half life of about 5 minutes in
human.
 The major enzyme responsible for insulin
degradation is hepatic glutathione insulin
dehydrogenase , which disrupts the hormone into
individual A & B chain

11. FUNCTIONS
 Insulin has anabolic & lipogenic effects
 Promotes storage of glucose in liver
 Activates enzymes to prmote glycolusis &
glycogenolysis
 Promote uptake & storage of aminoacids in the
form of protein
 Promote growth
 Also increases the amount of GLUT-4

12. THANK YOU