hormones

1. M.Prasad Naidu
MSc Medical
Biochemistry,
Ph.D.Research Scholar

2.  The acinar portion of pancreas has exocrine
function .
 Endocrine portion consists of islets of langerhans.

3.  Insulin is hetero dimeric polypeptide .
 Insulin gene is located on short arm of chromosome
11 .
 Insulin is synthesized as a preproinsulin ( 86 AA) .

5.  The location of 3 disulfide bonds is invarient & the
A & B chains have 21 & 30 amino acids respectively
in most species .

6.  Substitutions occur commonly at 8 , 9 , 10
positions of the A chain thus this region is not
crucial for bioactivity .

7.  Zinc is present in high concentrations in B cell &
forms complexes with insulin & proinsulin .

8.  The proinsulin molecule undergoes a series of site
specific peptide cleavages that results in formation of
equimolar amounts of mature insulin & C –
peptide .
 Mature insulin & C peptide are present together in the
secretory granule .

9.  C – peptide is less susceptible than insulin to hepatic
degrdation , & it is a distinct molecule from an
antigenic stand point .

10.  Glucose level more than 70mg/dl stimulates insulin
synthesis , primarily by enhancing protein translation
& processing .

12.  Glucose is the key regulator of insulin secretion .

13.  Elevated plasma arginine is a potent stimulus for
insulin synthesis & secretion .
 The intestinal peptides cholecystokinin & gastric
inhibitory polypeptide increase insulin secretion in
response to oral glucose & so are referred to as
incretins .
 Chronic exposure to excessive levels of GH , cortisol,
placental lactogen , estrogen & progestins increase
insulin secretion .

14.  The synthesis & release of insulin are decreased
when there is scarcity of dietary fuels & also during
periods of stress .
 Alpha adrenergic agonist principally epinephrine ,
inhibits insulin release even when this process was
stimulated by glucose .
 Beta adrenergic agonists stimulate insulin release ,
probably by increasing the intracellular c AMP .

15.  Plasma half life of insulin is 3 – 5 minutes under
normal conditions .
 The major organs involved in insulin metabolism are
liver , kidney & the placenta .
 Insulin specific protease & hepatic glutathione
transhydrogenase are involved in degradation of
insulin .

16.  Effect on membrane transport : insulin promotes
glucose entry into muscle & adipose tissue .

17.  The transporter translocation is temperature &
energy dependent & is protein synthesis independent
.

18.  Insulin promotes amino acid entry into cells
particularly in muscle & enhances the movement of
K+ , Ca ++ , nucleotides , & inorganic phosphate .
These effects are independent of action of glucose
entry .

19.  Insulin increases hepatic glycolysis by
increasing the activity & amount of
glucokinase , phosphofructokinase , &
pyruvate kinase .

20.  Insulin decreases the activity of glucose 6
phosphatse , an enzyme found in liver not in
muscle.
 In skeletal muscle insulin stimulates glucose
entry through transporters & also increases
hexokinase II

21.  Insulin stimulates lipogenesis in adipose tissue .
1. By providing acetyl CoA & NADPH required for fatty
acid synthesis .
2. By maintaining normal level of enzyme acetyl CoA
carboxylase &
3. By providing glycerol involved in the TAG
synthesis .

22.  Lipogenesis is decreased in insulin deficiency .
 Increased fatty acids in circulation due to several
hormones unopposed action by insulin .
 Free fatty acids feed back inhibit their own synthesis
by inhibiting acetyl CoA carboxylase .
 Free fatty acids inhibit glycolysis at several steps &
stimulates gluconeogenesis .

23.  In liver & muscle insulin stimulates conversion of
glucose to glucose 6 phosphate ( by the actions of
glucokinase & hexokinase II resepectively .
 Glucose 6 phosphate is isomerized to glucose 1
phosphate & is incorporated into glycogen .
 Glycogen synthase is stimulated by insulin .
 Insulin inhibits the enzyme phosphorylase .
 The net effect of insulin on glycogen metabolism is
anabolic .

24.  Effect on glucose production : insulin decreases the key
gluconeogenic enzyme phospho enol pyruvate carboxy
kinase ( PEPCK ) by selectively inhibiting transcription
of gene that codes for mRNA for PEPCK .

25.  Effects on lipid metabolism : insulin is a potent inhibitor
of lipolysis in liver & adipose tissue .
 The above action is due to its ability to decrease cAMP
levels by activating phosphodiesterases .
 Insulin inhibits hormone sensitive lipase by the action of
phosphatase .
 Insulin affects the formation or clearance of VLDL & LDL
.

26.  Effects on protein metabolism : insulin promote protein
synthesis & retards protein degradation .
 The effect of insulin on protein synthesis in skeletal &
cardiac muscle & in liver are thought to be exerted at the
level of mRNA translation .
 Insulin shown to influence the synthesis of specific
proteins by effecting changes in corresponding mRNAs.

27.  Insulin activates a protein kinase path way that
results in activation of eIF – 4E , a factor essential
for the rate limiting step in protein synthesis .

28.  The regulation of mRNA synthesis is a major
action of insulin
 Insulin decrease transcription of PEPCK gene
leading to decreased amount of primary transcript
& of mature mRNA .
 More than 100 specifc mRNA by insulin.

30. • Effects on cell replication : insulin stimulates the
proliferation of number of cells in culture & it may
also be involved in the regulation of growth invivo .
• Insulin potentiats the ability of
1. Fibroblast growth factor ,
2. PDFG
3. EGF
4. Tumor promoting phorbol esters
5. PGF2 alpha
6. Vasopressin & cAMP analougues

31.  Insulin receptor along with PDGF & EGF has tyrosine
kinase activity .
 oncogene products involved in stimulating malignant
cell replication are also tyrosine kinases.
 Mammalian cells contain analogs of these oncogenes
( protooncogenes ) which may be involved in the
replication of normal cells .
 Expression of two protooncogene products , c –
fos , c – myc increases following addition of insulin &
PDGF to growth arrested cells .

36.  Glucagon is synthesized as precursor molecule.
 Half life of glucagon is 5 minutes .
 Glucagon is inactivated by liver an enzyme removes
1st
2 aminoacids from the amino terminal end by
cleaving Ser 2 & Gln 3 .
 Secretion of glucagon is inhibited by glucose .
 Glucagon binds to specific receptors & activates
adenylyl cyclase through G protein linked
mechanism .

37.  The cAMP activates phosphorylase , which
enhances glycogenolysis while inhibiting glycogen
synthase enzyme .
 Glucagon through cAMP , increase the rate of
transcription of mRNA from PEPCK gene &
stimulates synthesis of more PEPCK .
 PEPCK is the rate limiting enzyme gluconeogenic
pathway .
 Glucagon is a potent lipolytic agent , it increases
adipose cell cAMP & this activates hormone sensitive
lipase .

39.  D cells of islets synthesize large somatostatin
prohormone .
 The rate of transcription of prosomatostatin is gene is
markedly increased by enhanced cAMP .
 Somatostatin inhbits the release other islet cell
hormones through a paracrine action .
 In CNS it acts as neurotransmitter , in GIT it decreases
the delivery of nutrients into the circulation .

40.  Two families of GI horomones gastrin family &
secretin family .
 Gastrin family consists of gastrin &
cholecystokinin .
 Secretin family includes secretin , glucagon ,
gastric inhibitory polypeptide (GIP ) , Vasoactive
intestinal peptides .