 Introduction

 History
 Structure of insulin
 Biosynthesis
 Transport and catabolism
 Degradation
 Release of insulin
 Effects of insulin
 Clinical coorelations
 INTRODUCTION
Insulin
> protein hormone
> by islets of langerhans
> pancreas
Anabolic hormone
> growth & development
 HISTORY
• Canadian scientist
(1921)
–Fredrick G. Banting
–Charles H. Best

• extracted insulin
–from dog’s pancreas
STRUCTURE OF INSULIN
• Insulin
–Polypeptide hormone
–51 amino acids
–Two chains
• A chain 21 a.a.
• B chain 30 a.a.
• Held by interchange disulfide
bridges
 BIOSYNTHESIS OF INSULIN

 Synthesis of Preproinsulin.

 Conversion of preproinsulin to
proinsulin.

 Conversion of proinsulin to insulin.

GENETICS OF INSULIN SYNTHESIS

 The proinsulin precursor of

insulin is encoded by the INS
gene
Preproinsulin
M.W 11500
109 A.A
Proinsulin
M.W 9000
86 A.A
Insulin (21+30 A.A)
 CATABOLISM OF INSULIN
 Half life: 3-5 minutes
 Major organs of degradation
> Liver.
>Kidney.
>Placenta.
 50% of insulin removed in a single pass through
liver.
MECHANISM:
 Insulin specific protease.
 Glutathione insulin transhydrogenase (Insulinase
Regulation of Insulin Secretion
Correlation Between Plasma
Glucose & Insulin Levels
BIOLOGICAL EFFECTS OF
INSULIN
 Effect on carbohydrate
metabolism
 Glucose uptake

–Skeletal muscles

–Cardiac muscles

–Adipose tissue

–Mammary glands
 Effect on carbohydrate
metabolism (contd)
 Insulin independent tissues
 Brain
 RBC
 Testis
 Kidney
 Retina
 Intestinal mucosal cells
INSULIN MEDIATED
GLUCOSE UP TAKE
 CARBOHYDRATE METABOLISM
Metabolism Net Effect Effect on important enzyme

Glycolysis Increased Glucokinase

Phosphofructokinase
Pyruvate kinase
Glycogenesis Increased Glycogen synthatase
HMP shunt Increased Glucose 6-phosphate
dehydrogenase
Gluconeogenisis Decreased Pyruvate carboxylase
Phosphoenol Pyruvate
carboxylakinase
Glucose 6-phosphatase
Glycogenolysis Decreased Glycogen phosphorylase
 Lipid Metabolism
Metabolism Net effect Effect on important

enzymes
Lipogenesis Increased

DeNovo FA Synthesis Increased Acetyl CoA carboxylase

Avalbility of NADPH

Adipose tissue Increased Provide α-glycerol-3-PO4

Lipoprotein lipase

Lipolysis Decreased Hormone sensitive lipase

Ketogenesis Decreased HMG CoA synthetase

Lipoprotein Increased Utilization of VLDL & LDL

 Protein Metabolism
Metabolism Net Effect Effect on important
enzymes

Protein Increased RNA polymerase

synthesis Amino acids up take

Protein Decreased Transaminases

degradation Deaminases
CELL GROWTH &
DEVELOPMENT
• Promote cell growth and development

• Mediated by

• Epidermal growth factors.

• Platelet derived growth factor.

• Prostaglandings.
CLINICAL CORRELATIONS
Symptoms of Diabetes

• Frequent urination
• Thirst
• Hunger
• Weight loss (despite thirst,
hunger)
• Fatigue
• Vision impairment
Continued…
Continued…
LEPRECHAUNISM
 INSULINOMA
HYPERINSULINISM
Islet cell tumors, producing
such symptoms, are called
insulinomas
Insulin shock
High level of insulin.
Fall in blood glucose level.
CNS depression.

50-70 mg/dl CNS excitability

20-50 mg/dl CONVULSION&

COMA

< 20 mg/dl COMA

 HYPOGLYCAEMIA IN FETUS
OF DIABETIC MOTHER
Maternal blood glucose level.

 Transfered through placenta.

Fetal blood glucose level.

o β-cells of fetus secrete insulin.

o Saturation of placenta 30 mmol/L
o Hypoglycaemia
REFERENCES
• Lectures on “Endocrinology” by C.J.Baired
MD/PhD
• www.dtu.ox.ac.uk/4-T
• Lectures on “Signaling Through Insulin
Receptors” by Oksana Matveinko
• Wikipedia
• Arthur C.Guyton, John E.Hall, “Textbook Of
Medical Physiology” 11th edition Ch: 78 Page:961-
970
• Lectures By MA Hussain & ND Theise “ Stem-Cell
Therapy For Diabetes Mellitus”
Contd.

• Robert K.Murray, Daryl K.Granner, Victor

W.Rodwell, “Harper’s Illustrated Biochemistry”
27TH edition Ch:41 Page: 457
• John T.Hensen, Bruce M.Koeppen, “Netter’s Atlas
Of Physiology” 5th edition Ch:8 Fig. 8.19,8.20
• Robert B.Dunn “Kaplan Medical Physiology USMLE
Step 1 Lecture Notes” Section:9 Ch: 5 Page: 407-
413
• Insulin by Dr. Dana Armstrong and Dr. Allen
Bennett King
 Acknowledgements
Almighty Allah for giving me
audacity for my each step to its triumphant
completion
My Parents
Head of Biochemistry Department
Prof. Dr.Khawaja Muhammad Fayyaz
Dr. Shafqat Nazir
All teachers of biochemistry department
My Friends
Library staff
Projectionist
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