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Insulin presentation

This document summarizes key aspects of insulin including its history, structure, biosynthesis, transport, degradation, effects, and clinical correlations. It describes how insulin was first extracted from dog pancreases in 1921. Insulin is a polypeptide hormone composed of two chains that are held together. It regulates carbohydrate, lipid, and protein metabolism. Insulin increases glucose uptake and storage while decreasing gluconeogenesis. Clinically, insufficient insulin production can lead to symptoms of diabetes like frequent urination.

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 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)
Human proinsulin and its conversion to insulin.
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)  In s u lin in d e p e n d e n t t is s u e s  B r a in  RB C  Te s t i s  K id n e y  R e t in a  In t e s t in a l m u c o s a l c e lls
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
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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 Dr. Shafqat Nazir All teachers of biochemistry department My Friends Library staff Projectionist
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