APPLIED ASPECT OF INSULIN

& GLUCAGON

DR. LAXMIKANTA SAY

Actions of Insulin on Adipose Tissue

1. Glucose entry 2. Fatty acid synthesis 3. Glycerol phosphate

synthesis 4. Triglyceride

deposition 5. Activation of

Lipoprotein lipase 6. K+ uptake

Muscle 1. Glucose entry 2. Glycogen synthesis 3. Aminoacid uptake 4. Protein synthesis 5. Protein catabolism 6. release of

Gluconeogenic AA 7. Ketone uptake 8. K+ uptake

Liver

1. Ketogenesis 2. Protein synthesis 3. Lipid synthesis 4. Glucose output 5. Glycogen synthesis 6. Glycolysis

APPLIED ASPECT OF INSULIN

HYPERGLYCEMI

A

HYPOGLYCEMIA

DIABETES MELLITUS

It is a syndrome of impaired carbohydrate , fat and protein metabolism caused by either due to lack of insulin secretion or decrease sensitivity of tissues to insulin.

Type I Type II

PREDISPOSING FACTORS

Hereditary – Definite genetic susceptibility

Age Obesity - BMI >30 - Insulin resistance - ability of insulin to move

glucose into fat & muscle

Clinical Types 1. Pre – diabetic or Potential

Diabetic - Strong genetic predisposition 2. Latent Diabetic - Stress, Obesity 3. Clinical Diabetes 4. Overt diabetes mellitus - Juvenile & MODY 5. Secondary DM - diseases associated - Pancreatitis (destruction of B- cells),

Acromegaly, Cushing’s syndrome

Clinical Features

1. Hyperglycemia 2. Glycosuria 3. Polyuria 4. Dehydration 5. Polydipsia 6. Polyphagia 7. Weight Loss

Pathophysiology of DM Protein Catabolism

Aminoacidaemia

Gluconoegenesis

NH2 of AA converted to Urea & Excretion

Urinary N2 excretion (Negative N2 balance)

CELLULAR DEHYDRATION

Loss of Cellular K+ to ECF

Urinary excretion of K +

Carbohydrate metabolism

HYPERGLYCEMIAGlycosuria

Polyuria (Osmotic Diuresis)Wate & electolyte loss

DEHYDRATIONHaemoconcentration, Blood Volume

Peripheral Circulatory Failure Tissue Hypoxia

Decreased B.PCerebral Blood Flow , Renal Flow Anuria

Renal Failure

COMA & DEATH (metabolic acidosis, renal failure, cerebral

ischemia, dehydration)

Fat Metabolism Lipogenesis

Mobilization depot fats

HYPERTRIGLYCERIDAEMIA

Fatty Liver Decreased Oxidation FFA

Acetly Co-A

Ketogenesis

Ketonaemia

Ketonuria

Natriuresis

COMPLICATIONS OF DM 1. Microvascular abnormality - diabetic retinopathy, - diabetic nephropathy 2. Macrovascular abnormality - accelerated atheroscelerosis - stroke, MI 3. Neuropathic abnormality - diabetic neuropathy - atherosclerotic insufficiency - reduced resistance to infection - chronic ulceration & gangrene

Diagnosis

Urine glucose Fasting plasma glucose and insulin GTT

GTT

CLINICAL COMPARISION FEATURE TYPE I TYPE II

Age at onset < 40 yrs >40 yrs

Body mass Low to normal Obese

Ketosis & Acidosis

High Incidence Rare

Plasma insulin Low or absent Normal to high

Plasma glucagon

High , can be suppressed

High , resistant to suppression

Plasma glucose High High

Insulin sensitivity

Normal Reduced

Therapy Insulin Wt. loss , drugs , insulin

HYPOGLYCEMIA 1. Iatrogenic - insulin overdose -Overdose of oral hypoglycemic

agents

2. β – cell adenoma

3. Functional - delayed secretion of insulin - severe exercise

HYPOGLYCEMIA90

75

60

45

30

15

0

Plasma glucose in mg/dl

Inhibition of insulin secretion

Glucagon , GH , Epinephrine secretion

Cortisol secretion , Cognitive dysfunction

Lethargy

Coma , Convulsion

Permanent brain damage , Death

GLUCAGON

Linear polypeptide, Mol. Wt. 3485

Produced by A – cells of Pancreatic islets & upper GI

29 AA Human Preproglucagon

found in Pancreas, GI & Brain

Product of single mRNA

ACTION OF GLUCAGONLiver - Glycogenolysis - Gluconeogenesis - Inhibit storage of TG - KetogenicAdipose tissue - Lipolysis+ve ionotropic actionIncrease blood flow to kidneyBile secretionInhibits gastric acid secretion

REGULATION OF SECRETION Stimulators Inhibitors Low glucose Amino acids CCK , Gastrin Cortisol Exercise Infections &

stress β adr.

stimulation Acetylcholine

High glucose Somatostatin Secretin FFA Ketones Insulin α adrenergic

stimulation GABA

Blood glucose regulation

Hyperglycemia

Hypoglycemia

Insulin

Glucagon

THANK YOU