Insulin and its Uses

Insulin is a peptide hormone produced by beta cells of the pancreatic islets, and it is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells.

1. INSULIN BY Dr. Muhammad Saifullah Punjab Medical College, Faisalabad

2. PANCREAS - INTRODUCTION The pancreas is the largest of the digestive glands present inside the abdominal cavity. The pancreas, in addition to its digestive functions , secretes two important hormones, insulin and glucagon , that are crucial for normal regulation of glucose, lipid, and protein metabolism.

3. HISTOLOGY OF THE PANCREAS The pancreas is composed of two major types of tissues: Acini , which secrete digestive juices into the duodenum. Islets of langerhans , which secrete insulin and glucagon directly into the blood.

4. INSULIN Insulin is a small protein ; human insulin has a molecular weight of 5808 . It is composed of two amino acid chains, connected to each other by disulfide linkages.

5. INSULIN RECEPTOR The insulin receptor is a combination of four subunits held together by disulfide linkages: Two alpha subunits that lie entirely outside the cell membrane Two beta subunits that penetrate through the membrane, protruding into the cell cytoplasm. NOTE: The insulin binds with the alpha subunits on the outside of the cell.

6. SYNTHESIS OF INSULIN Insulin is synthesized in the pancreas within the β-cells  of the islets of Langerhans. The endocrine portion accounts for only 2% of the total mass of the pancreas. Within the islets of Langerhans, beta cells constitute 65–80% of all the cells.

7. SYNTHESIS OF INSULIN

8. METABOLIC EFFECTS OF INSULIN Effect on Carbohydrate Metabolism Effect on Fat Metabolism Effect on Protein Metabolism & Growth

9. EFFECT ON CARBOHYDRATE METABOLISM Insulin promotes muscle glucose uptake and metabolism between meals. Storage of glucose as glycogen in non-exercising muscle. Insulin promotes liver uptake & storage of glucose as glycogen after the meal which is later released back when required.

10. EFFECT ON CARBOHYDRATE METABOLISM Insulin promotes conversion of excess glucose into fatty acids and inhibits gluconeogenesis in the liver. Lack of effect of insulin on glucose uptake and usage by the brain because brain cells can use glucose even without insulin . In other cells insulin increases glucose transport into and glucose usage by most other cells of the body.

11. EFFECT ON FAT METABOLISM Insulin promotes fat synthesis . Insulin promotes storage of fat in the adipose cells. Insulin deficiency causes lipolysis of storage fat and release of free fatty acids which is used for energy. Insulin deficiency increases plasma cholesterol and phospholipid concentrations.

12. EFFECT ON PROTEIN METABOLISM & GROWTH Insulin promotes protein synthesis and storage by stimulating transport of many of the amino acids into the cells and promoting translation of mRNA. Insulin deficiency causes protein depletion and increased plasma amino acids . Insulin and growth hormone interact synergistically to promote growth because it is anabolic hormone.

13. MECHANISM OF INSULIN SECRETION

14. FACTORS AFFECTING INSULIN SECRETION INCREASE INSULIN SECRETION DECREASE INSULIN SECRETION Increased blood glucose Increased blood free fatty acids Increased blood amino acids Gastrointestinal hormones ( gastrin ) Glucagon, growth hormone, cortisol Parasympathetic stimulation; A.Ch β -Adrenergic stimulation Sulfonylurea drugs ( glyburide , tolbutamide ) Decreased blood glucose Fasting Somatostatin Alpha-Adrenergic activity Leptin

15. ABNORMALITIES RELATED TO INSULIN: INSULINOMA: Pancreatic β-cell tumour Characterized by recurrent hypoglycemia. Usually small tumour (<5mm in Dia ) 10% Malignant Diagnosed by CT-scan, MRI or Ultrasound Treatment: Medical: Diet control + Insulin inhibitors ( Diazoxide ) Surgical: Resection

16. DIABETES MELLITUS Clinical syndrome characterized by hyperglycemia due to absolute or relative deficiency of Insulin. Types Type I – IDDM is usually due to autoimmune disease leading to β-cell destruction. Type II – NIDDM is due to relative Insulin deficiency due to Insulin resistance and impaired β-cell dysfunction.

17. COMPLICATIONS OF DIABETES: Microvascular : Retinopathy Nephropathy Diabetic foot Macrovascular : Myocardial infarction Cerebral infarction Peripheral vascular Ischemic disease MANAGEMENT: Strict diabetic control via: Diet Drugs Exercise

18. REFERENCES Guyton and Hall Textbook of Medical Physiology 12th edition Davidson's Principles and Practice of Medicine Wikipedia, the free encyclopedia