Insulin is a polypeptide hormone composed of two chains of amino acids that is produced by beta cells in the pancreas. It plays an important role in regulating blood glucose levels. Insulin binds to receptors on cells and signals the translocation of glucose transporters to cell membranes, allowing glucose uptake. It also stimulates the synthesis of enzymes involved in glycolysis. Diabetes occurs when the body does not produce enough insulin or the cells ignore the insulin signal, resulting in high blood glucose levels. The document provides details on the structure, function, biosynthesis and role of insulin.

1. Insulin
Amit Kumar Singh
Lovely Professional University
Department of Applied Medical Science
Clinical Biochemistry 28.01.2017

2. CONTENTS:
• Introduction
• History of Insulin
• Structure of Insulin
• Biosynthesis
• Transport and Catabolism
• Degradation
• Release of Insulin
• Effects of Insulin
• Clinical Coorelations
• Conclusion
• References

3. INSULIN
 Insulin (Insula-Island)is a Polypeptide hormone
produced by the β-cell of islets of Langerhans of
Pancreas.
 “Langerhanse(1869) first of all identified β-cell in islets of
pancreas. Human pancreas contain about two million islets
of langerhans.
 Human insulin molecular weight 5.7 kd is composed o 51
amino acids arranged in two peptide chains designated as A
B that are helt togather two inter chain disulfide linked.
 Chain A contain-21 amino acid
 Chain B contain-30 amino acid
 Gene for coding insulin is located on chromosome 11.

4. HISTORY
 Insulin is a polypeptide hormone which was the hormone to be
discovered by “Fredric Banting and Dr.Charles best” from the
pancreas of Dog, The two scientist were awarded the Nobel
prize.
 The molecular formula of human insulin is C254H377O75N65S6
which consist of 51 amino acid. In 1952 “Fredrick Sangar
“examined that insulin was made up o two chain of amino acid A
B.The two chain are parallel to each other and bounded by
disulfide bond.
 In 1977 “Rosalyn sussman Yalow “developed Radioimmunoassay
for Insulin for which she received the novel prize. The first
commercial insulin came from Cow(Bovine) and Pig
(Porcine).
 In 1977 “Herbert Boyer” using “Escherichia coli “produce the
first genetically engineering synthetic human insulin in the
laboratory.

5. BIOSYNTHESIS OF INSULIN
Insulin is synthesized as a large precursor polypeptide chain
the pre-pro insulin . It has 109 amino acid. It is rapidly
converted to pro-insulin in the endoplasmic reticulum
by removal of leader sequence of 23 amino acid residue.
The proinsulin with 86 amino acid is transported to Golgi
apparatus where it is cleaved by protease. The site specific
cleavage is done by enzyme named as “prohormone
convertase 1 and 2”.The C-peptide or connecting peptide
with 33 amino acid is removed. (The number of amino acid
in C peptide may vary according to species). Now insulin
has 53 amino acid :the extra two amino acid are removed by
caroxypeptidase H and insulin with 51 amino acid is thus
formed.

8. Insulin Mechanism of action
 lt is now recognized that insulin binds to specific
plasma membrane receptors present on the target
tissues, such as muscle and adipose. Three distinct
mechanisms of insulin action are known:
1. induction of transmembrane signals (signal
transduction)
2. Glucose transport across the membrane
3. Induction of enzyme synthesis

9. 1. Insulin receptor mediated signal trans'duction Insulin
receptor
 Insulin receptor :
 lt is a tetramer consisting of4 subunits of two types and is designated as
 A α2 β2. α subunit i s extracellulaar contains insulin binding site.
 it contains insulin binding site. The β-subunit is a transmembrane
protein which is activated by insulin. The cytoplasmic domain of β-
subunit has tyrosine kinase activity.

11. The bindingo f insulin to insulin receptors signals the translocation of vesicles
containing glucose transporters from intracellular pool to the plasma
membrane. The vesicles fuse with transemembrane recruiting the glucose
transporters.The glucose transporters re responsible for the insulin-mediated
uptake of glucose by the cells. As the insulin level falls, the glucose transporters
move away from the membrane to the intracellular pool for storage and recycle
2. Insulin-mediated glucose transport :

12. • Glucokinase
• Phosphofructokinase
• Pyruvate kinase
3.Insulin mediated enzyme synthesis
Hexokinase
Phosphofructokinase
glucose Glycolysis
ATP
ADP
glucose-6-phosphate
Phosphoglucose Isomerase
fructose-6-phosphate
ATP
ADP
fructose-1,6-bisphosphate
Aldolase
glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
Triosephosphate
Isomerase
Glycolysis continued
Glyceraldehyde-3-phosphate
Dehydrogenase
Phosphoglycerate Kinase
Enolase
Pyruvate Kinase
glyceraldehyde-3-phosphate
NAD+
+ Pi
NADH + H+
1,3-bisphosphoglycerate
ADP
ATP
3-phosphoglycerate
Phosphoglycerate Mutase
2-phosphoglycerate
H2O
phosphoenolpyruvate
ADP
ATP
pyruvate

15. Glucose 6-phosphate
has 3 fates.

16. Diabetes mellitus
Diabetes mellitus is caused when a high amount of
glucose gets stored in the body and low level of insulin
is secreted that cannot converted glucose into
glycogen.Blood glucose level is maintained by the
Insulin. There are tree types of diabetes mellitus-
1-Type –I
2-Type-II
3-Gestational diabetes

17.  Type-I Diabetes(Insulin dependent diabetes mellitus
IDDM) It used to be called juvenile-onset diabetes, is a
disease caused when the body synthesized a little amount
of insulin. It generally affected a person before the age of 20
year.The gene responsible for the disorder characteristics f
type I is MHC class II reasons on chromosomes 6 at the
staining region 6p21.
 Type-II Diabetes (Non insulin dependent diabetes
mellitus NIDDM)is a lifelong disease in which the body
fails to synthesize insulin. It usually occurs in adult aged
over 40 year. type 2 diabetes can still cause major health
complications, particularly in the smallest blood vessels in
the body that nourish the kidneys, nerves, and eyes. Type 2
diabetes also increases your risk of heart
disease and stroke.

18. Conclusion
• Polypeptide hormone(Pncrease)
• PrePro insulin
• 2 Chain of Amino acids(A Chain, B Chain)
• Mechanism of Action
• Diabetes Melitus

19. Refferences:
 U.Satyanarayana,U.Chakrapani,Biochemistry,fourth
edition,2015.
 DM Vasudevan,Sreekumari S,Text Book of
biochemistry; 4th edition ,2004.
 http://www.medbio.info/horn.
 http://www.slideshare.net/aishahadalicia/insulin-
and-its-mechanism-of-action.
 https://en.wikipedia.org/wiki/Insulin