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Hormones that affect energy metabolism © Michael Palmer 2014 Langerhans’ islets in the pancreas produce insulin and glucagon © Michael Palmer 2014 A little bit of history: The purification of insulin— the problem © Michael Palmer 2014 The purification of insulin—Banting’s solution © Michael Palmer 2014 Historical side note: Norman Bethune, Banting’s famous classmate © Michael Palmer 2014 Structure of insulin and its precursors (1) © Michael Palmer 2014 Structure of insulin and its precursors (2) © Michael Palmer 2014 Sequences of human, swine, and bovine insulins © Michael Palmer 2014 Insulin secretion in the β-cell is controlled by glucose and triggered by membrane depolarization © Michael Palmer 2014 The sulfonylurea receptor controls an associated potassium channel © Michael Palmer 2014 KATP channels also regulate the tone of smooth muscle cells © Michael Palmer 2014 Tolbutamide promotes closing of the KATP channel © Michael Palmer 2014 The insulin receptor is a receptor tyrosine kinase © Michael Palmer 2014 Insulin receptor first phosphorylates itself and then a number of insulin receptor substrate proteins © Michael Palmer 2014 Insulin effects on glycogen synthesis © Michael Palmer 2014 The role of insulin in glucose transport © Michael Palmer 2014 Insulin promotes glucose uptake by increasing the surface exposure of GLUT 4 transporters © Michael Palmer 2014 Transcriptional regulation by insulin © Michael Palmer 2014 Other hormones © Michael Palmer 2014 Glucagon and epinephrine act via G-proteincoupled receptors © Michael Palmer 2014 The glucagon and epinephrine receptors activate adenylate cyclase and protein kinase A © Michael Palmer 2014 Metabolic effects of protein kinase A © Michael Palmer 2014 Glucocorticoids and thyroid hormones act on nuclear hormone receptors to activate transcription © Michael Palmer 2014 DNA binding by thyroid hormone receptors © Michael Palmer 2014 Metabolic effects of glucocorticoid hormones ● induction of enzymes for glycogen synthesis, glycogen breakdown, and gluconeogenesis ● induction of enzymes for protein breakdown, supplying substrates for gluconeogenesis ● induction of adrenergic receptors …overall, glucocorticoids increase blood glucose Glucocorticoid receptor agonists and antagonists © Michael Palmer 2014 Control of food intake by leptin © Michael Palmer 2014
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