Insulin
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Transcript of Insulin
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INSULIN AND ORAL HYPOGLYCEMIC AGENTS
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DIABETES Diabetes Insipidus (DI) Diabetes Mellitus (DM)
Metabolic disorder –
Hyperglycemia
Glycosuria
Hyperlipemia
Negative nitrogen balance
Ketonaemia
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Pathological changes
- Thickening of capillary basement membrane- Increase in vessel wall matrix- Cellular proliferation
- Complications
- Early atherosclerosis- Retinopathy- Neuropathy
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Types of DM
Type I insulin dependent diabetes mellitus(IDDM), juvenile onset diabetes mellitus.
Type IA(autoimmune) Type IB(idiopathic)
Type II noninsulin dependent diabetes mellitus(NIDDM), maturity onset diabetes mellitus
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Insulin
Two chain polypeptide- 51 amino acid
A- chain- 21 amino acids B-chain- 30 amino acids
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Regulation of Insulin Secretion Chemical Hormonal Neural
ACTION OF INSULIN
Carbohydrate
Protein
Fat metabolism
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Mechanism of action Tyrosin kinase receptor
Fate of insulinOrally- degraded in g.i.t
i.v- metabolised in liver
Types of insulin preprationsConventional Highly purified
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According to purification method
Single peak insulin Monocomponent insulins
HUMAN INSULINS
rDNA technology in E.coli
Enzymatic modification of porcine insulin
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Indication of Human insulin Insulin resistance Allergy to conventional preprations Injection site lipodystrophy Short term use of insulin in diabetics During pregnancy
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Reactions of insulin Hypoglycaemia Local reactions Allergy Edema
Drug interactions
USES OF INSULINDMDiabetic ketoacidosis(Diabetic Coma)
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Insulin lack
Hyperglycaemia Ketosis
GlycosuriaAcidosis ketonuria Impairment of
glucose entry into brain
Loss of electrolytes
Intracellular K+
depletion
Loss of fixed cations in urine
Loss of water
Hyperosmolarity of bloodIntracellulardehydration
Osmotic diuresisVomiting
Hyperventilation
Dehydration
Hypotension,Shock,tachycardia
Impairment of consciousness
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Hyperosmolar (Non ketotic hyperglycaemia)
Insulin Resistance Acute
Chronic
Infection,trauma,surgery,emotional stressketoacidosis
Conventional preprations
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ORAL HYPOGLYCAEMIC DRUGS
Drugs lower the blood glucose level
Effective orally
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Sulfonyl Ureas
Biguanides
Meglitinide Analogues
First generationTolbutamidechlorpropamide
Second generationGlibenclamide(glyburide)GlipizideGliclazideGlimepiride
PhenforminMetformin
RepaglinideNateglinide
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Thiazolidinediones Rosiglitazone Pioglitazone
α-Glucosidase Inhibitors Acarbose Miglitol
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SULFONYLUREAS
These agents promote the release of insulin from β-cells (secretogogues);
Mechanism: These agents require functioning β-cells, they
stimulate release by blocking ATP-sensitive K+ channels resulting in depolarization with Ca+2 influx which promotes insulin secretion.
They also reduce glucagon secretion and increase the binding of insulin to target tissues.
They may also increase the number of insulin receptors
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BIGUANIDES (Insulin Sensitizers) work by improving insulin target cell response; the
biguanides & thiazolidinediones.
Biguanides: it increases glucose uptake and utilization by target
tissues
Mechanism: Metformin reduces plasma glucose levels by inhibiting
hepatic gluconeogenesis. It also slows the intestinal absorption of sugars. It also
reduces hyperlipidemia (↓LDL & VLDL cholesterol and ↑ HDL).
It is the only oral hypoglycemic shown to reduce cardiovascular mortality.
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THIAZOLIDINEDIONES (Glitazones)
These agents are insulin sensitizers, they do not promote insulin secretion from β-cells but insulin is necessary for them to be effective
Mechanism of Action:
These agents act through the activation of peroxisome proliferator-activated receptor-γ (PPAR-γ).
Agents binding to PPAR-γ result in increased insulin sensitivity is adipocytes, hepatocytes and skeletal muscle.
Accumulation of subcutaneous fat occurs with these agents.
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MEGLITINIDE ANALOGUES
Mechanism: These agents bind to ATP sensitive K+channels like
sulfonylureas acting in a similar fashion to promote insulin secretion however their onset and duration of action are much shorter.
They are particularly effective at mimicking the prandial & post-prandial release of insulin.
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α-Glucosidase Inhibitors
oligosaccharides monosaccharides
Acarbose also inhibits pancreatic amylase.
hydrolyses
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Glucagon
Single chain polypeptide- 29 amino acid
MW- 3500
Regulation ↑ glucose levelFFA and ketone bodies
Action- opposite to insulin(hormone of fuel mobilization)Secretion ↑ during fasting
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MOAActivates adenylyl cyclase ↓ ↑cAMP
USES-hypoglycaemia due to insulin or oral hypoglycaemics-cardiogenic shock-diagnosis of pheochromocytoma
Liver Fat cells heart
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