Insulin – Metabolic Actions

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 Kpumping 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.
Exam Question
 

INSULIN – METABOLIC ACTIONS: 

EFFECTS ON CARBOHYDRATE METABOLISM:

  • Increased Glycogenesis.
  • Increased glycolysis
  • By inducing phosphofructokinase & pyruvate kinase enzymes.
  • 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”
  • By increasing GLUT-4 on cell membrane
  • Transport occurs against concentration gradient. 

In Liver:

  • Insulin-Independent glucose entry.
  • Induction of glucokinase – “Glucose trapping” 

EFFECTS ON LIPID METABOLISM

  • Induces Lipogenesis by enzyme acetyl CoA carboxylase.
  • Increases triglyceride synthesis by inducing lipoprotein lipase.
  • Reduces lipolysis by inhibting hormone-sensitive lipase.
  • Reduces ketogenesis (“Anti-lipolytic action”)

EFFECTS ON PROTEIN METABOLISM

  • Stimulates anabolism –
  • Increasing the rate of synthesis of mRNA
  • Inhibits catabolism –
  • Increases active transport of amino acids into tissues.

EFFECTS ON ELECTROLYTES

  • Causes Hypokalemia 

EFFECTS OF INSULIN ON VARIOUS TISSUE:

On Adipose Tissue:

  • Increased glucose entry converted 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 K+ uptake

On Liver:

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