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.
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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