IntroductionHistoryStructure of insulinBiosynthesisTransport and catabolismDegradationRelease of insulinEffects of insulinClinical coorelations

INTRODUCTIONINTRODUCTIONInsulin

> protein hormone > by islets of langerhans > pancreas

Anabolic hormone > growth & development

HISTORYHISTORY• 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 Proinsulin M.W 9000 M.W 9000

86 A.A 86 A.A

Insulin (21+30 A.A)Insulin (21+30 A.A)

Human proinsulin and its conversion to insulin.

CATABOLISM OF CATABOLISM OF INSULININSULINHalf 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 Regulation of Insulin SecretionSecretion

Correlation Between Plasma Correlation Between Plasma Glucose & Insulin LevelsGlucose & Insulin Levels

BIOLOGICAL EFFECTS OF BIOLOGICAL EFFECTS OF INSULININSULIN

EffectEffect on carbohydrate on carbohydrate metabolismmetabolism

Glucose uptakeGlucose uptake

–Skeletal musclesSkeletal muscles

–Cardiac musclesCardiac muscles

–Adipose tissueAdipose tissue

–Mammary glandsMammary glands

Effect on carbohydrate metabolism (contd)

Insulin independent tissues

Brain

RBC

Testis

Kidney

Retina

Intestinal mucosal cells

INSULIN MEDIATED INSULIN MEDIATED GLUCOSE UP TAKEGLUCOSE UP TAKE

CARBOHYDRATE METABOLISMMetabolism Net Effect Effect on important enzyme

Glycolysis Increased Glucokinase PhosphofructokinasePyruvate kinase

Glycogenesis Increased Glycogen synthatase

HMP shunt Increased Glucose 6-phosphate dehydrogenase

Gluconeogenisis Decreased Pyruvate carboxylasePhosphoenol Pyruvate carboxylakinaseGlucose 6-phosphatase

Glycogenolysis Decreased Glycogen phosphorylase

Lipid MetabolismLipid Metabolism

MetabolismMetabolism Net Net

effecteffect

Effect on important Effect on important

enzymesenzymes

LipogenesisLipogenesis IncreasedIncreased

DeNovo FA DeNovo FA SynthesisSynthesis

IncreasedIncreased Acetyl CoA carboxylaseAcetyl CoA carboxylaseAvalbility of NADPHAvalbility of NADPH

Adipose tissueAdipose tissue IncreasedIncreased Provide Provide αα-glycerol-3-PO-glycerol-3-PO44

Lipoprotein lipaseLipoprotein lipase

LipolysisLipolysis DecreaseDecreasedd

Hormone sensitive lipaseHormone sensitive lipase

KetogenesisKetogenesis DecreaseDecreasedd

HMG CoA synthetaseHMG CoA synthetase

Lipoprotein Lipoprotein IncreasedIncreased Utilization of VLDL & LDLUtilization of VLDL & LDL

Protein MetabolismProtein MetabolismMetabolism Net Effect Effect on important

enzymes

Protein synthesis

Increased RNA polymeraseAmino acids up take

Protein degradation

Decreased TransaminasesDeaminases

CELL GROWTH & DEVELOPMENT

• Promote cell growth and development

• Mediated by

• Epidermal growth factors.

• Platelet derived growth factor.

• Prostaglandings.

CLINICAL CORRELATIONSCLINICAL CORRELATIONS

Symptoms of Diabetes

•Frequent urination•Thirst•Hunger•Weight loss (despite thirst,

hunger)•Fatigue•Vision impairment

Continued…Continued…

Continued…Continued…

LEPRECHAUNISMLEPRECHAUNISM

INSULINOMA INSULINOMA HYPERINSULINISMHYPERINSULINISM

Islet cell tumors, producing Islet cell tumors, producing such symptoms, are calledsuch symptoms, are called

insulinomasinsulinomas

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 HYPOGLYCAEMIA IN FETUS OF DIABETIC FETUS OF DIABETIC

MOTHERMOTHER Maternal blood glucose level.Maternal blood glucose level.

Transfered through placenta.Transfered through placenta. Fetal blood glucose level.Fetal blood glucose level.

o ββ-cells of fetus secrete insulin.-cells of fetus secrete insulin.o Saturation of placentaSaturation of placenta 30 mmol/L 30 mmol/Lo HypoglycaemiaHypoglycaemia

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 ParentsHead of Biochemistry Department Dr. Shafqat Nazir All teachers of biochemistry department My Friends Library staff Projectionist

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