Insulin presentation
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IntroductionHistoryStructure of insulinBiosynthesisTransport and catabolismDegradationRelease of insulinEffects of insulinClinical coorelations
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INTRODUCTIONINTRODUCTIONInsulin
> protein hormone > by islets of langerhans > pancreas
Anabolic hormone > growth & development
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HISTORYHISTORY• Canadian scientist
(1921)–Fredrick G. Banting –Charles H. Best
• extracted insulin – from dog’s pancreas
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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
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BIOSYNTHESIS OF INSULIN
Synthesis of Preproinsulin.
Conversion of preproinsulin to proinsulin.
Conversion of proinsulin to insulin.
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GENETICS OF INSULIN SYNTHESIS
The proinsulin precursor of insulin is encoded by the INS gene
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Preproinsulin M.W 11500
109 A.A
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Proinsulin Proinsulin M.W 9000 M.W 9000
86 A.A 86 A.A
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Insulin (21+30 A.A)Insulin (21+30 A.A)
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Human proinsulin and its conversion to insulin.
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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).
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Regulation of Insulin Regulation of Insulin SecretionSecretion
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Correlation Between Plasma Correlation Between Plasma Glucose & Insulin LevelsGlucose & Insulin Levels
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BIOLOGICAL EFFECTS OF BIOLOGICAL EFFECTS OF INSULININSULIN
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EffectEffect on carbohydrate on carbohydrate metabolismmetabolism
Glucose uptakeGlucose uptake
–Skeletal musclesSkeletal muscles
–Cardiac musclesCardiac muscles
–Adipose tissueAdipose tissue
–Mammary glandsMammary glands
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Effect on carbohydrate metabolism (contd)
Insulin independent tissues
Brain
RBC
Testis
Kidney
Retina
Intestinal mucosal cells
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INSULIN MEDIATED INSULIN MEDIATED GLUCOSE UP TAKEGLUCOSE UP TAKE
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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
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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
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Protein MetabolismProtein MetabolismMetabolism Net Effect Effect on important
enzymes
Protein synthesis
Increased RNA polymeraseAmino acids up take
Protein degradation
Decreased TransaminasesDeaminases
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CELL GROWTH & DEVELOPMENT
• Promote cell growth and development
• Mediated by
• Epidermal growth factors.
• Platelet derived growth factor.
• Prostaglandings.
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CLINICAL CORRELATIONSCLINICAL CORRELATIONS
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Symptoms of Diabetes
•Frequent urination•Thirst•Hunger•Weight loss (despite thirst,
hunger)•Fatigue•Vision impairment
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Continued…Continued…
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Continued…Continued…
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LEPRECHAUNISMLEPRECHAUNISM
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INSULINOMA INSULINOMA HYPERINSULINISMHYPERINSULINISM
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Islet cell tumors, producing Islet cell tumors, producing such symptoms, are calledsuch symptoms, are called
insulinomasinsulinomas
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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
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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
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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”
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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
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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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