Insulin – Metabolic Actions

INSULIN – METABOLIC ACTIONS: 

EFFECTS ON CARBOHYDRATE METABOLISM:

Overall effect:

• Decrease blood glucose level.
• Increase utilization of glucose

Mechanism of action:

• Increased Glycolysis.
• By inducing phosphofructokinase & pyruvate kinase enzymes 
• Increased Glycogenesis.
• By glucose conversion to storage form glycogen, in liver & muscle.
• Inhibition of gluconeogenesis.
• By inactivating pyruvate carboxylase, PEP carboxykinase, fructose 1, 6 – bisphosphatase, glucose – 6 – phosphates

Glucose uptake:

• In Muscle and Adipose tissue:
• “Insulin-facilitated diffusion” 
• Increasing glucose transporter (GLUT-4) on cell membrane
• Transport across cell membrane against glucose gradient. 

In Liver:

• Indirect action – Insulin-independent glucose entry.
• By inducing glucokinase, “Glucose trapping” occurs.
• Forms glucose – 6 – phosphate.

EFFECTS ON LIPID METABOLISM:

Overall effect:

• Reducing release of fatty acids from stored fat

Mechanism:

• Induces lipogenesis –
• By enzyme acetyl coA carboxylase
• Increases Triglyceride synthesis –
• By inducing lipoprotein lipase.
• Reduces lipolysis –
• By inhibiting hormone-sensitive lipase.
• Reduces free fatty acids & glycerol – 
• Reduces ketogenesis (“Anti-lipolytic action”)

EFFECT ON PROTEIN METABOLISM

• Stimulates anabolism
• Protein synthesis.
• By increasing mRNA synthesis rate.
• Inhibits catabolism
• Protein breakdown.
• By increasing amino acids active transport into tissues.

EFFECT ON POTASSIUM: 

• Causes hypokalemia.
• By increasing Na2+– K+-ATPase activity in cell membranes
• Stimulating K+ pumping into cells.
• Mainly in muscle & adipose tissue.

EFFECTS OF INSULIN ON VARIOUS TISSUE:

General Effects:

• Increased cell growth.

On Adipose tissue:

• Increased glucose entry & conversion to triglycerides
• Increased fatty acid synthesis.
• Increased lipogenesis.
• Increased glycerol phosphate synthesis.
• Activation of lipoprotein lipase.
• Increased clearance of VLDL & chylomicron.
• Inhibition of lipolysis.
• Inhibition of hormone-sensitive lipase

On Muscle:

• Increased glucose entry
• Increased glycogen synthesis
• Increased amino acid uptake
• Increased protein synthesis in ribosomes
• Decreased protein catabolism
• Decreased release of gluconeogenic amino acids
• Increased ketone uptake
• Increased K+ uptake, thus hypokalemia 

On Liver:

• Decreased ketogenesis.
• Increased protein synthesis.
• Increased lipid synthesis.
• Decreased glucose output.
• By ↓ing gluconeogenesis & ↑ing glycolysis).
• Increased glycogen synthesis.
• Inhibits glycogenolysis.