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INSULIN

BIOCHEMISTRY

mprasadnaidu
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INSULIN

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  1. Insulin & oral hypoglycaemic M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.

  2. Diabetes mellitus :- It is a group of heterogenous disorder in which carbohydrate metabolism is ↓, while that of proteins & lipids are ↑. Types :- Type I - insulin dependent DM Type II – non insulin dependent DM Type III – DM occurs by other disorders Type IV – gestational DM

  3. Insulin :- Chemistry , biosynthesis & secretion :- Chemistry : - Insulin is made up of 86 aminoacids , It contain A chain – 21 AA, B chain – 30 AA, Connecitng Peptide – 35 AA. Biosynthesis :- Preproinsulinproinsulin Insulin + C peptide Secretion :- Glucose transport to β cell by GLUT 2 glucose transporter, it undergoes further metabolism, it generated ATP. Which inhibit the activity of K+ CHANNELS. The inhibition of K+ channel induces β cell membrane depolarisation, opening of voltage dependent Ca2+ channel & stimulates insulin secretion.

  4. Pharmacological actions :- • Carbohydrate metabolism : • ↑glycogenesis ↓ glycogenolysis • Protein metabolism : • ↓ protein break down ↑ • Fat metabolism : • ↑ lipogenesis ↑fatty acid synthesis.

  5. Newer insulin preparations : • Insulin syringes • Portable pen injections • Insulin pumps • Biodegradable microspheres • Inhaled insulins • Therapeutic uses :- • Type 1 diabetes – NPH + Regular Insulin • Type 2 diabetes - Regular Insulin • Diabetic ketoacidosis – Tr. IV fluids, Kcl, sodium bicarbonate, phoshate • Non ketonic hyperglycemic • Emergency treatment of hyperkalaemia

  6. Adverse effects :- • Hypoglycaemia • Lipodystrophy • Allergic manifestation • Insulin resistance • Edema

  7. Oral hypoglycaemic drugs :- Classification :- Sulfonylureas : 1st generation - Tolbutamide Chlorpropamide 2nd generation – Glibenclamide Glipizide Gliclazide Glimepiride Meglitinide analogues :- Repaglinide Nateglinide

  8. Biguanides :- Metformin Phenformin Alfa glucosidase inhibitors :- Acarbose Miglitol Thiazolidinediones : Rosiglitazone Pioglitazone

  9. Sulfonylureas :- MOA :- Sulfonylureas acts on beta cells, stimulating insulin secretion and thus reducing blood glucose levels. Drugs reuce the permeability of K+ by competitively blocking the sulfonylureas receptors present on ATP sensitive K+ channels , causing depolarisation, Ca2+ entry and insulin secretion. Adverse effects :- Hypoglycaemia Weight gain, nausea, vomiting, diarrhoea, constipation , agranulocytosis, hypersensitivity, cholestatic jaundice.

  10. PK :- Absorbed orally, high plasma protein bindint(90-98%) Metabolized in liver , excreted in urine Duration of action – 6-12 hr It croses placental barrier it caused hypoglycaemia at birth CI :- Pregnancy Gestational diabetes

  11. Drug interactions :- Drugs that potentiate the effects of sulfonylureas– Oral anticoagulants, ketoconazole, chloramphenicol (-) metabolism Salicylates, sulfonamides , clofibrate – displace protein binding sites Drugs that decrease the effects of sulfonylurease: Phenobarbitone, phenytoin , rifampicin – decrease metabolism corticosteroids, thiadides, estrogens - Biguanides :- ↑ uptake and utilization of glucose in skeletal muscle reduce insulin resistant (-) renal hepatic gluconeogenesis ↓ glucose absorption from GIT ↓ Plasma glucagon levels

  12. Corticosteroids Classification :- Glucocorticoids : Short acting – Hydrocortisone Intermediate acting – Prednisolone Methyl prednisolone Triamcinolone Long acting - Betamethasone Dexamethasone Meneralocorticoids :- Desoxycorticosterone acetate Fludrocortisone aldosterone

  13. Mechanism of actions :- Corticoids bind to specific receptor in the cytoplasm , the drug Receptor complex is transported into the nucleous where it binds to specific Sites on DNA and regulates the synthesis of new proteins that bring about The hormone effects . Pharmacological actions :- Mineralocorticoids highly effects on Na+, k+ and fluid balance Glucocorticoids highly effects on carbohydrate, protein, fat and other. Metabolic effects :- Carbohydrate – promote gluconeogenesis Protein- enhance protein break down Fat –lipolysis, redistribution of fat

  14. Antiinflammatory and immunosuppressive effects :- • Supress development of inflammatory response to all types of stimuli inhibit bothLate and early manifestations of inflammation. • Supress cell mediated immunity, prevent manifestations of allergy • Ca 2+ metabolism – (-) intestinal absorption & enhance renal excretion of ca2+ • CVS :- • Skeletal muscle :- hypocritism, hypercritism • CNS :- euphoria • Stomach :- increase gastric secretion • Lymphoid tissue and blood cells :- increase destruction of lymphoid cells, increase no. of RBC, neutrophils, platelets.

  15. Therapeutic uses :- • Replacement therapy : • Acute adrenal insufficiency • Chronic adrenal insufficiency • Congenital adrenal hyperplasia • Pharmacotherapy: • Arthritides : NSAIDS + glucocorticoids • Rheumatoid arthritis • Osteoarthritis • Rheumatic fever • Gout • Collagen diseases – SLE, nephrotic syndrome, glomerulonethritis • Severe allergic reactions – angioneuotic edema, urticaria and serum sickness

  16. Autoimmune diseases : haemolyticanaemia, thrombocytopenia, • chronic hepatitis • Bronchial asthma : status asthmaticus, acute asthma excerbation • Other lung diseases : Pulmonary edema aspiration penumonia • Infective diseases : tuberculosis, severe lepra reaction • Eye diseases : keratitis, iridocyclitis, iritis, allergic conjuctivitis, prevent blindness • Skin diseases : exfoliative dermatitis, stevenshohnson syndrome • Intestinal diseases : ulcerative colitis, coeliac disease • Cerebral edema : • Malignancies : acute lymphatic leukemia, hodgkins & breast carcinoma • Organ transplantation and skin allograft : liver, kidney, heart transplantation. • Shock :

  17. Adverse effects :- • Mineralocorticoids– hypokalemic alkalosis, edema, raise in BP • Glucocorticoids :- • Cushing’s habitus • Hyperglycaemia • Muscular weakness • Delayed healing • Peptic ulceration • Osteoporosis • Galucoma • Growth retardation • Foetal abnormalities

  18. Psychiatric disturbances • Suppression of hypothalamo pituitary adrenal axis • Fragile skin , purple striae • Contraindications :- • Peptic ulcer • DM • HT • Viral and fungal infections • Tuberculosis & other infections • Osteoporosis • Psychosis • Epilepsy • CHF • Renal failure

  19. THANK U

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