09. Blood Glucose

• the body can store unlimited fat but we have a capacity for glycogen
• carbohydrate is the bodys primary energy source - brains only source
• glucose remain in blood until taken up by cells
• hyperglycaemia

  • polyuria, thirst, weight loss
  • -> neuropathy, heart disease, diabetic coma
• hypoglycaemia:

  • irritability, fatigue, cravings
  • -> loss of consciousness, weight gain, brain abnormalities
• islet of langerhans has alpha cells which produce glucagon and beta cells which produce insulin

  • alpha cells surround beta cells
  • also delta cells -> somatostatin
• insulin is a polypeptide that allows circulating glucose to be used by cells

  • hypoglycaemic agent
• insulin is processed from pre-pro insulin

  • c chain gets cleaved out by endopeptidase in vesicles
  • insulin held in vesicle by zinc
• beta cells recognise we have too much blood glucose -> insulin production
• 1. blood high in glucose passes by beta cell
  2. glucose moves into cell via GLUT2 (bidirectional)
  3. glucokinase phosphorylates glucose, preventing it leaving and allows glucose to keep entering cell
  4. used to generate ATP
  5. as ATP increases, the ATP sensitive potassium channel closes, depolarising membrane
  6. calcium channels open - exocytosis of insulin vesicles
• insulin receptor has intrinsic kinase activity

  • amino acids -> protein
  • glucose -> glycogen
  • storage of triglycerides
• insulin acts in muscle to promote GLUT4 translocation to cell surface, allows muscle to take up glucose

  • also promotes activity of lipoprotein lipases, enabling tissue to bring in fats ad store them
• IRS-1 allows changes to the cytoskeleton to enable the GLUT4 molecules to be moved to the cell surface
• glucagon has antagonistic activity to insulin

  • secreted in response to low blood sugar
  • promotes gluconeogenesis and glycogenolysis
  • increases ketogenesis and lipolysis
  • hyperglycaemic agent
• GLP1 is produced when food is in the stomach - binds to beta cells producing insulin

  • useful for treating diabetes
  • broken down quickly by DPP, clinically we prevent this by producing analogues that resist this
• SGLT2 is found primarily in the kidney proximal tubule - transports sodium and glucose into the cells, and GLUT2 transports glucose out of the cells and into the blood

  • SGLT2 inhibitors can be used to block the activity of GLUT2
  • more glucose excreted