Insulin

Insulin

Mechanism of action:Insulin acts by binding with insulin receptor.Insulin receptor (IR) is a glycoprotein of 3,50,000 MW.It has 2 subunits:
[A]2 α-subunites:Lying outer aspect of cell membrane.
[B]2 β-subunits:Which are transmembranous.Tyrosine kinase is related to β-subunit.  
      
Steps:
Binding of insulin with α-subunite of insulin receptor
Auto-phosphorylation of β-subunit
Activation of β-subunit
Stimulation of some enzyme in the cell and they perform all the activities of insulin.

Pharmacological effects/Adverse effects:

Type of metabolism
Liver
Skeletal muscle
Adipose tissue
Carbohydrate metabolism
↑Glycogenesis.
↑Glycolysis.
↓Glycogenolysis. 
↓Gluconeogenesis
↑Glucose uptake
↑Glycolysis
↑Glycogenesis
↓Glycogenolysis
↑Glucose uptake
↑Fatty acid synthesis
↓Lipolysis
Protein metabolism

↑Amino acid uptake
↑Protein synthesis

Fat metabolism


↑Glycerol synthesis
↑Synthesis of triacylglyceride
↓Liolysis

Indications:

1)      IDDM.
2)      NIDDM-When OHA fail.
3)      DM associated with complications:
·         DM+Ketoacidosis.
·         DM+Nephropathy.
·         DM+Retinopathy.
·         DM+Gangrene(Sever infections)
4)      DM in pregnancy(because OHA can cross placenta & teratogenic)
5)      DM pt during(before 1 day)and after surgery.
6)      Hyperkalaemia.

Insulin is administered:

1)      Sub.cutaneous→  hour before breakfast to prevent sever hypoglycemia.
2)      I.V→in case of emergency.

Preparations of insulin:

1)      Bovine insulin(from cow)
2)      Procine insulin(from pork)
3)      Human insulin(from man)

Adverse effects/Complication of insulin/Hazared of insulin:

1)      Hypoglycemia:Hypoglycaemic reaction,hypoglycaemic shock.
2)      Insulin allergy.
3)      Lipodystrophy.
4)      Insulin edema.
5)      Rebound hyperglycemia.
6)      Insulin resistance.
7)      Obesity.
8)      Hypokalaemia.
9)      Alopecia.(Loss of hair)

Contraindications:

1)      Hypertension taking β blocks.
2)      Insulin resistance case.
3)      Hypersensitizing to insulin.
    
Classify anti-diabetic drugs:

[A]According to onset & duration of a action:

Types
Example
Onset of action
Duration of action
Route of adm
1.Rapid acting insulin(soluble insulin)
*Insulin lispro
*Insulin aspart
*Insulin glulisine
Within 15-60 min
3-5 hours
IV
2.Short acting insulin(Soluble insulin)
*Regular insulin
*Natural insulin
Within 30 min
5-8 hours
IV
3.Termediate acting insulin
*NPH or Isophane
*Insulin zinc suspension (Lente)
Within 1-2 hours
12-24 hours
Subcutaneous
4.Long acting insulin
*Crystalline insulin zinc suspension
*Protamine zinc insulin suspension
*Insulin glargine
4-6 hours
>24 hours
Subcutaneous
5.Mixture of insulin:(Biphasic insulin)
*Soluble(25%)+ Crystalline(75%)
*Crystalline+Isophane
*Soluble(50%)+Isophane(50%)
1 or 2 hours
24 hours
Subcutaneoous

[B]According to source:

1)      Mixed species insulin:70% bovin + 30% porcine insulin(& other combination)
2)      Monospecies insulin(Porcine):
·         Actrapid.
·         Monotard.
·         Semitard.
3)      Newer insulin preparation:
·         Human insulin:
ü  Enzyme modified porcine insulin(EMP).
ü  Chain recombinant bacterial insulin(CRB).

·         Human proinsulin.

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