Metabolic Effects of Insulin on
Cellular Uptake of Glucose
Supachai A. Basit, RMT, PhD
Overview
• Four major organs
play a dominant role
in fuel metabolism
• Integration of energy
metabolism is
controlled prim...
Insulin
• Polypeptide hormone
produce by the beta cells
of the islet of Langerhans
of the pancreas
• Most important hormon...
Structure of Insulin
• 51 amino acids
• Polypeptide A and B, linked together by a
disulfide bridges
• Intramolecular disul...
Synthesis of Insulin
• Two inactive precursors  cleaved to form
the active hormone plus the C-peptide
• C-peptide  essen...
Stimulation of Insulin Secretion
• Insulin and glucagon
secretion is closely
coordinated at the
islet of Langerhans
• Secr...
Stimulation of Insulin Secretion is
Increased by: Glucose
• ß cells contain Glut-2
transporters and have
glucokinase activ...
Stimulation of Insulin Secretion is
Increased by: Amino Acids
• Ingestion of protein
causes a transient
rise in plasma ami...
Stimulation of Insulin Secretion is
Increased by: Gastrointestinal Hormones
• Cholecytoskinin and gastric-
inhibitory pept...
Inhibition of Insulin Secretion: Epinephrine
• Scarcity of dietary fuels and during
the period of stress
• Direct effect o...
Metabolic Effects of Insulin:
Carbohydrates Metabolism
• Promotes storage in 3
tissues
• In liver & muscle, increase
glyco...
GLUT-4 Transport Protein
Metabolic Effects of Insulin:
Lipid Metabolism
Decrease TAG
Degradation
• Insulin inhibits
hormone-sensitive
lipase
• Insu...
Metabolic Effects of Insulin:
Protein Synthesis
• Insulin stimulates
the entry of amino
acids into cells, and
protein synt...
Insulin binds to specific, high
affinity receptors in the cell
membrane of most tissues
including liver, muscle and
adipos...
Membrane Effects of Insulin
• Glucose transport increases in the presence of insulin as this
promotes the recruitment of i...
Characteristics of Glucose Transport in
Various Tissues
Receptor Regulation
• Binding of insulin is
followed by internalization
of the hormone-receptor
complex
• Once inside the ...
Metabolic Effects of Insulin
Metabolic Effects of Insulin
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Metabolic Effects of Insulin

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Metabolic Effects of Insulin

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Metabolic Effects of Insulin

  1. 1. Metabolic Effects of Insulin on Cellular Uptake of Glucose Supachai A. Basit, RMT, PhD
  2. 2. Overview • Four major organs play a dominant role in fuel metabolism • Integration of energy metabolism is controlled primarily by the actions of insulin and glucagon
  3. 3. Insulin • Polypeptide hormone produce by the beta cells of the islet of Langerhans of the pancreas • Most important hormone coordinating the use of fuels by tissues • Metabolic effects  anabolic – Favoring the synthesis of glycogen, triacylglycerols and protein
  4. 4. Structure of Insulin • 51 amino acids • Polypeptide A and B, linked together by a disulfide bridges • Intramolecular disulfide bridge between amino acid residues of the A chain
  5. 5. Synthesis of Insulin • Two inactive precursors  cleaved to form the active hormone plus the C-peptide • C-peptide  essential for proper insulin folding
  6. 6. Stimulation of Insulin Secretion • Insulin and glucagon secretion is closely coordinated at the islet of Langerhans • Secretion is regulated so that the rate of hepatic glucose production is kept equal to the use of glucose by peripheral tissues
  7. 7. Stimulation of Insulin Secretion is Increased by: Glucose • ß cells contain Glut-2 transporters and have glucokinase activity and thus can phosphorylate glucose in amounts proportional to its actual concentration in blood • Ingestion of CHO rich meal leads to a rise in blood glucose, which is a signal for insulin secretion and decrease glucagon synthesis and release
  8. 8. Stimulation of Insulin Secretion is Increased by: Amino Acids • Ingestion of protein causes a transient rise in plasma amino acids level, which in turn induces the secretion of insulin • Elevated plasma arginine stimulates insulin secretion
  9. 9. Stimulation of Insulin Secretion is Increased by: Gastrointestinal Hormones • Cholecytoskinin and gastric- inhibitory peptide increased insulin secretion • Incretins • Released from SI in response to oral glucose and cause anticipatory rise in insulin levels • This may account for the fact that the same amount of glucose given orally induces a much greater secretion of insulin that is given intravenously
  10. 10. Inhibition of Insulin Secretion: Epinephrine • Scarcity of dietary fuels and during the period of stress • Direct effect on energy metabolism causing glycogenolysis and gluconeogenesis • Can override the normal glucose- stimulated release of insulin • In emergency situation, the sympathetic nervous system largely replaces the plasma glucose concentration as the controlling influence over ß cells secretion
  11. 11. Metabolic Effects of Insulin: Carbohydrates Metabolism • Promotes storage in 3 tissues • In liver & muscle, increase glycogen synthesis • In muscle and adipose, increase glucose uptake by more GLUT-4 • Insulin decreased the production of glucose by inhibiting glycogenolysis and gluconeogenesis
  12. 12. GLUT-4 Transport Protein
  13. 13. Metabolic Effects of Insulin: Lipid Metabolism Decrease TAG Degradation • Insulin inhibits hormone-sensitive lipase • Insulin acts by promoting the dephosphorylation and hence inactivation of enzymes Increase TAG Synthesis • Insulin increases the transport and metabolism of glucose into adipocytes providing substrate for glycerol-3-phosphate for TAG synthesis • Increases the lipoprotein lipase, thus providing fatty acids for esterification
  14. 14. Metabolic Effects of Insulin: Protein Synthesis • Insulin stimulates the entry of amino acids into cells, and protein synthesis through activation of factors required for translation
  15. 15. Insulin binds to specific, high affinity receptors in the cell membrane of most tissues including liver, muscle and adipose tissue. The following should be considered 1. Insulin receptor 2. Signal transduction 3. Membrane effects of insulin 4. Receptor regulation MechanismofInsulinAction
  16. 16. Membrane Effects of Insulin • Glucose transport increases in the presence of insulin as this promotes the recruitment of insulin-sensitive glucose transporter (GLUT-4) from a pool located in intracellular vesicles
  17. 17. Characteristics of Glucose Transport in Various Tissues
  18. 18. Receptor Regulation • Binding of insulin is followed by internalization of the hormone-receptor complex • Once inside the cell, the insulin is degraded in the lysosomes • The receptors may be degraded but most are recycled to the cell surface

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