· Intro: summary and mechanism
· Effects on adipose, liver, muscle
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Summary |
· Peptide hormone · Synthesised and stored in islet β-cells · Release stimulated by ↑BSL more than ↑amino acids and ↑FFA Anabolic and pro-inflammatory effects in adults, growth factor in utero · ↑ de novo lipogenesis (DNL), ↓lipolysis |
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Cellular mechanism |
· Insulin receptor: o Tyrosine kinase o 2 x extracellular α-subunits, 2 x intracellular β-subunits · Binding of insulin: o Autophosphorylation and activation of TK activity o Signalling via PI3K (metabolic) and MAPK (inflammation etc.) pathways |
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In adipose |
· ↑GLUT4 expression -> ↑glucose uptake and trapping -> ↑glycerol synthesis · ↑endothelial LPL activity-> ↑FFA uptake from VLDL and chylomicrons · ↓HSL activity -> ↓TAG breakdown (opposite if catecholamines) · ↑activity of pyruvate dehydrogenase, Acetyl-CoA carboxylase -> ↑DNL -> ↑TAG storage o i.e. glucose -> pyruvic acid -> acetyl CoA -> fatty acid |
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In liver |
· ↑Hexokinase activation -> ↑glucose uptake via GLUT2 · ↑DNL via ↑PDH and ↑Acetyl-CoA carboxylase activity · ↑synthesis and release of lipoproteins (transports lipids to tissues) · ↑synthesis of cholesterol (HMGCoA reductase) · Inhibit synthesis of ketones (acetoacetate, β-OH-butyrate, acetone) o Excess Acetyl CoA undergoes DNL rather than ketogenesis |
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In skeletal muscle |
· Once glycogen is replete: ↑DNL (minor) |