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 tissues-
muscle, 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