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Regulation of carbohydrate

metabolism

Insulin

Glucagon

Somatostatin Catecholamines

Cortisol

Growth hormone Thyroxin

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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

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Endocrine Pancreas

Insulin

Glucagon

Somatostatin Pancreatic Polypeptide

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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

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Insulin

Hormone of abundance

Polypeptide

Anabolic hormone

Structure of Insulin:

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Insulin Actions

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Insulin effect on carbohydrate

metabolism

Increased uptake of glucose by body tissues-muscle, liver, etc

Storage of glucose in the form of glycogen in

liver and muscle Inactivates liverphosphorylase

Increase glucokinase activity

Increased activity ofglycogen synthase Stimulates conversion of excessive glucose

into fatty acids

Inhibits gluconeogenesis

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Effect of insulin on intracellular

glucose concentration in muscles

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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

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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 andketone bodies

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Effect of pancreatectomy on blood

glucose, fatty acids and acetoacetate

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Effect of insulin on protein metabolism

Increases amino acid uptake

Increases translation & transcription

Inhibits protein catabolism Inhibits gluconeogenesis

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Other actions

Actions on K - insulin & glucose cause inwardmovement of K ion

Stimulates growth

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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

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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

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Insulin Deficiency- Diabetes Mellitus

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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

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Metabolic abnormalities of type 1 DM

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Classification of diabetes mellitus

Diabetes mellitus type 1: autoimmune or

idiopathic

Diabetes Mellitus type 2: insulin resistance

Old classification: IDDM & NIDDM

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Treatment of DM

Insulin preparations

Oral hypoglycemic drugs

- Biguanides- Phenformin & Metformin- Sulfonylureas- Glipizide, Glibenclamide

- Thiozolidinediones- Rosiglitazone

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Insulin preparations

Bovine, porcine, recombinant insulin

Short, intermediate and long-acting

Subcutaneous, intravenous Nasal, rectal, trans peritoneal

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Insulin excess

Hypoglycemia