BIOSYNTHESIS OF INSULIN

 Beta-cells of islets of Langerhans synthesize insulin

 Insulin has an AB heterodimeric structure with one intrachain (A6-A11) and two interchain
disulfide bridges (A7-B7 and A20-B9)
 Insulin is synthesized as preprohormone (preproinsulin)
o Molecular wt = 11, 500
o Prototype for peptides that are processed from larger precursor molecules

A chain of insulin
(21 amino acids)
ß-cells Single-chain 86-
Peptidase in
amino acid precursor B chain of insulin
“PROINSULIN” Golgi complex INSULIN
polypeptide: (30 amino acids)
 CLEAVE
"PREPROINSULIN" (SPLIT)
C- peptide

 Mature C-peptide and insulin molecule  stored together and co-secreted from secretory
granules in ß-cells.
 Glucose – key regulator if insulin secretion by pancreatic ß-cells
o By enhancing protein translation and processing.

INSULIN SECRETION:

Glucose enters beta cells via GLUT

glucophospholyration by
glucokinase  glucose-6-
phosphate metabolism via
glycolysis  pyruvate ATP 
inhibit ATP-sensitive K-channel 
membrane depolarization  Ca
channel opens  influx of Ca 
insulin secretion
INSULIN RECEPTOR:

 Belong to receptor tyrosine kinase

family
 Exists as dimer
 Insulin substrate receptor(IRS)
 Non-IRS kinases

INSULIN ACTION:
CONTROL OF INSULIN RELEASE:

1. Basal secretion
2. Enhanced release when blood glucose level rise
a. Biphasic with initial increase lasts for 10 mins followed by second more prolonged rise
reaches a plateau 2-3 hrs later
3. Mechanisms involved in the release of insulin are believed to include
a. Intracellular second messengers cyclic adenosine monophosphate (camp) ,and
b. Phospholipase C