Dr.

Niranjan Murthy H L Asst Prof of Physiology SSMC, Tumkur

Regulation of carbohydrate metabolism

Insulin Glucagon Somatostatin Catecholamines Cortisol Growth hormone Thyroxin

 Blood glucose levels: 80-140 mg/dL FBS: 60-90 mg/dL Importance of blood glucose regulation- brain, retina and gonads 100gm of glycogen is stored in liver Liver acts as GLUCOSTAT

Endocrine Pancreas
Insulin Glucagon Somatostatin Pancreatic Polypeptide

Islet of Langerhans
2% of volume of pancreas 1-2 millions 76 x 175 m collections A cells- Glucagon B cells- Insulin (60-75%) D cells- Somatostatin F cells- Pancreatic Polypeptide

Insulin
Hormone of abundance Polypeptide Anabolic hormone Structure of Insulin:

Biosynthesis, secretion & Fate

Preproinsulin Proinsulin Insulin & C peptide C peptide levels- index of B cell function Half life- 5 min Insulinase Proteases in endosomes

Insulin Actions

Insulin effect on carbohydrate metabolism

Increased uptake of glucose by body tissuesmuscle, liver, etc Storage of glucose in the form of glycogen in liver and muscle Inactivates liver phosphorylase Increase glucokinase activity Increased activity of glycogen synthase Stimulates conversion of excessive glucose into fatty acids Inhibits gluconeogenesis

Effect of insulin on intracellular glucose concentration in muscles

Glucose transporters
Facilitated diffusion (GLUTs) Secondary active transporters (SGLTs) Glucose Transporters (GLUTs) GLUT 4- muscle & adipose tissue- insulin & exercise sensitive GLUT 2- basolateral membrane & B cells SGLT 1 & 2- intestine & kidney

Insulin effect on lipid metabolism

Lipid sparing Converts excess glucose to fatty acids Activates lipoprotein lipase Inhibits hormone-sensitive lipase Promotes glucose transport into adipose cells Insulin lack increases cholesterol levels and ketone bodies

Effect of pancreatectomy on blood glucose, fatty acids and acetoacetate

Effect of insulin on protein metabolism

Increases amino acid uptake Increases translation & transcription Inhibits protein catabolism Inhibits gluconeogenesis

Other actions
Actions on K - insulin & glucose cause inward movement of K ion Stimulates growth

Mechanism of insulin action

Insulin receptor: Glycoprotein, 340000, tetramer, two & two subunits Intracellular portion of subunit has tyrosine kinase activity Insulin binding cause autophosphorylation of subunits Phosphoinositol 3-kinase promote protein anabolic activity Half life of receptor is 7 hours

Mechanism of insulin secretion

Increased blood glucose Influx of glucose into B cells Phosphorylation of glucose by glucokinase Glucose-6-phosphate ATP production Inhibition of ATP-sensitive K+ channels Depolarization Influx of Ca2+ Release of insulin

Insulin Deficiency- Diabetes Mellitus

Hyperglycemia Disorders of protein metabolism Disorders of fat metabolism Clinical features: polydipsia, polyuria and polyphagia Loss of weight Increased atherogenesis Diabetic ketoacidosis Hyperosmolar coma Microvascular and macrovascular complications

Metabolic abnormalities of type 1 DM

Classification of diabetes mellitus

Diabetes mellitus type 1: autoimmune or idiopathic Diabetes Mellitus type 2: insulin resistance Old classification: IDDM & NIDDM

Treatment of DM
Insulin preparations Oral hypoglycemic drugs - Biguanides- Phenformin & Metformin - Sulfonylureas- Glipizide, Glibenclamide - Thiozolidinediones- Rosiglitazone

Insulin preparations
Bovine, porcine, recombinant insulin Short, intermediate and long-acting Subcutaneous, intravenous Nasal, rectal, trans peritoneal

Insulin excess
Hypoglycemia