Definition of hormones
Pancreas
Intro of insulin
Chemistry
Biosynthesis
Action of insulin
Metabolic effect on insulin
Factors effect insulin secretion
Disorders related to insulin hormone
Treatment
Brand name of insulin in market
3. Content
• Definition of hormone.
• Pancreas.
• Introduction of insulin
• Chemistry.
• Biosynthesis.
• Action of insulin.
• Factors Effect insulin secretion.
• Disorders.
• Brand name of insulin in market.
4. Hormones
• Definition:
“These are chemical messengers needed in small
amount to accelerate or inhibit the metabolic
activities of target organ.”
• Human body secretes about 50 different types of
hormones.
• Hormones can be classified on the basis of their nature
e.g. Proteins/polypeptides,steroid,Amino acids hormones
5. Pancreas:
• PANCREAS contains both exocrine &
endocrine cells.
• Roughly 99% of the cells of the
pancreas are arranged in clusters called
ACINER CELLS.
• Endocrine cells → ISLETS OF
LANGERHANS,1-2% of pancreatic
tissues.
6.
7. ISLETS OF LANGERHANS:
• Also termed as ISLAND OF
LANGERHANS.
• Irregular shaped patches of endocrine
tissues present in pancreas.
• Named for German Physician PAUL
LANGERHAN…discovered in 1969.
8. CELLS OF ISLETS OF LANGERHANS:
• Four types of cells.
1. α-cells (glucagon)
2. β-cells (insulin)
3. D- cells (somatostatin))
4. F-cells (PPP)
11. HISTORY
• 1921 → Dr.Fredrick Banting
(R) & Charles Best (L)
discovered insulin.
• From dog’s pancreas.
• 1932 → received → Noble
prize.
• From Latin →Insula»Island.
12. Characteristics:
• PolyPeptide Hormone.
• Secreted by β-cells in the islets of langerhans
of pancreas.
• Regulates the metabolic activity of
carbohydrates , fats and Proteins.
• Anabolic Hormone.
• 1st hormone » isolated, purified and synthesis.
• 1st hormone to sequence.
• 1st Hormone to be produced By DNA
technology.
14. Chemistry of insulin
• 1956 → chemical structure of insulin was given by
Sanger.
• Human Hormone contains 51 Amino acids → arranged in
2 polypeptide chains
1. Chain A = 21 AA.
2. Chain B = 30 AA.
• Two interchain Disulfide bridge; A7—B7 & A20—B19
• Intrachain disulfide link in chain; A6—A11.
17. Biosynthesis of insulin
• Synthesis of insulin Gene located on 11th
chromosome.
• Synthesis of preproinsulin (11500 Mw & 109
AA) in RER.
• Conversion of preproInsulin to proinsulin
(9000 Mw & 86 AA) in ER.
• Conversion of proinsulin into insulin & C-
peptide in Golgi apparatus.
• C-peptide is a connecting peptide that
connects a and beta chains. It has no
biological activity.
18. Amount of insulin secretion:
• About 45–50 Units secreted daily
by human pancreas.
• Normal value 20–30 Units/ml.
19. Half life of insulin
• Biological half-life of insulin is 5-6
min.
• Insulinase degraded insulin in liver &
kidney by cleavage of S–S bond.
21. Action of insulin
Summary of how insulin works.😏
• Elevated levels of glucose in the blood stimulates cell
of pancreas to ↑ insulin secretion into the blood.
• The insulin circulates the body, within minutes,
stimulates the liver and muscle cells to take up
glucose from the blood, As a result blood glucose
level fall.
22. Action on insulin
• To initiate it’s effects on target
cells, insulin 1st binds with and
activates a membrane receptor
protein.
• The insulin receptor is a tetramer
made up of 2 a-subunits that lie
outside Thecell membrane and 2
b-subunits that penetrate the cell
membrane and protrude into the
cytoplasm.
23. Cont’d
• When insulin binds with the alpha subunits on
the outside of the cells, portion of the beta
subunits protruding into the cell become
autophosphorylated.
• Thus,the insulin receptor is an example of an
enzyme-linked receptor.
• Autophosphorylation of beta subunits of the
receptor activaties a local tyrosine kinase
,which in turn cause phosphorylation of
multiple other intracellular enzymes including
a group called insulin-recepyor substrates (
IRS).
24. Cont’d
• The net effect is to activate some of
these enzymes while inactivating
others.
• This way, insulin directs the
intracellular metabolic machinery
to produce the desired effects on
the carbohydrates,fats and protein
metabolism.
• This causes the cells to become
more permeable to glucose.
25. Metabolic effect of insulin
Effect on carbohydrate metabolism:-
a) In liver and muscles insulin increases glycogen
synthesis
b) In muscle and adipose insulin increase glucose
uptake by increasing the number of glucose transporters
(GLUT-4) in the cell membrane
c) In liver insulin inhibits the production of glucose by
inhibiting glucogenolysis and gluconeogenesis
26. Cont’d
Effect on lipid metabolism:-
a) Insulin reduces fatty acid release by inhibiting activity
of hormone-sensitive lipase.
b) Insulin converts glucose into adipocytes providing
glycerol 3-phosphate substrate for TAG.
c) Expression of gene for lipoprotien lipase increases by
insulin results in fatty acids for esterification of glycerol.
27. Cont’d
Effect on protein metabolism:-
a) Insulin stimulates entry of amino acids into cells and
protein synthesis through activation of factors required for
translation initiation
31. Diabetes mellitus:
• Definition:
. Metabolic disorder characterzed by
high blood glucose level associated with
another manifestation.
• Diabetes → polyuria
• Mellitus → Honey
• Named coined by Thomas William →
sweetness urine from diabetic in 1675.
• Multi organ damaged → kidney, eyes, blood
vessels..
32. Types;
• There are two types of diabetes
mellitus.
1. Type I DM
2. Type 2 DM
33. Type I DM:
• Due to deficiency of insulin
• Cause: destruction of beta cells in islets
of langerhans by T-cells & auto-
antibodies.
• Early onset…… < 20 age → juvenile
diabetes.
• Also know as insulin dependent
diabetes.
34. Type 2 DM:
• Due to insulin resistance ( failure of insulin
receptors to give response to insulin).
• Body is unable to use insulin.
• About 90% of diabetic patients have type 2
DM.
• Usually occur < 40 years.
• Also called non-insulin-dependent
diabetes mellitus (NIDDM).
35.
36. Sign & symptoms
Both types of diabetes , if not controlled
,share many similar symptoms, including:
• Increased thirst.
• Frequent urination.
• Extreme hunger.
• Irritability and other mood changes
• Fatigue & weakness.
• Blurred vision.
38. Drugs used for diabetes mellitus;
There are so many drugs used for diabetes
mellitus. Some of which are following:-
• Glocophage - metformin HCL.
• Alpha-glucosidase inhibitors - Acarbose.
• Meglitinides - nateglinide.
• Combination of sulfonylureas plus
metformin - known by generic names of
the two drugs
39. Insulinoma
• Hyper-secretion of insulin.
• Cause: Due to tumors of beta cells in islets of
langerhans.
• Typical cause : insulin resistance → to be linked to
type 2 DM.
42. Drugs Used For Insulinoma
• Diazoxide is the drug of choice because it inhibits
insulin release from the tumor. Adverse effects must
be treated with hydrochlorothiazide. In patients not
responsive to or intolerant of diazoxide (10%),
somatostatin may be indicated to prevent
hypoglycemia