Metabolism after a meal

• High insulin

  • increase of: → hyperglycemia in T2DM

    • glucose oxidation
    • glycogen synthesis
    • fat synthesis
    • protein synthesis
    • uptake of glucose by muscle + fat (not liver) → because of GLUT 4 receptor

  • decrease of:

    • glucose production
    • fat breakdown → fat in bloodstream with T2DM

  • produced in pancreas (beta cells)

    • main target organs: liver, adipose tissue, muscle

    

Fasting metabolism

• High glucagon

  • Increase of
    • glycogenolysis → only from the liver, not in the muscle (because nog G6phosphatase)!
    • gluconeogenesis → together these are called hepatic glucose production
    • ketogenesis → production of ketone bodies (for brain and muscles)
    • lypolysis
  • Produced in pancreas (alpha cells)
  • Liver is the main target organ

  

  Molecular level of insulin signaling

  • Fast effects
    • GSK3 is phosphorylated. No more inhibition of glycogen of synthase
    • GLUT4 translocation to the cell membrane
      • expressed in muscle + adipose tissue
  • Slow effects
    • ERK activation causes increased gene expression

Glucose is taken up from the intestinal luman by sodiu/glucose transport protein 1 and exported into the blood by GLUT2

GLUT 3: only expressed in brain → high affinity → so mostly used in case of hypoglycemia

GLUT 2: low affinity but high capacity → so mostly used after a meal.

Glycolysis regulation

All regulated enzymatic reactions are irreversible

• glucose → G6P, uses ATP

  • hexokinase: in other tissue → high affinity, low capacity, inhibited by G6P.

  • glucokinase: in liver + beta cells → low affinity, high capacity, stimulated by insulin

    • in beta cells there is a glucose sensor: ATP is used: ATP/ADP ratio chagnes → changec K channel.

    

  • in MODY patients there is a mutation in glucokinase. Higher levels of glucose needed for activity glucokinase → ATP/ADP ratio remains the same for longer → no release of insulin yet.

• PFK-1: fru-6-P → fru-1,6-BP
  • Low concentration of ATP activate PFK-1, high concentrations inhibit it
  • insulin increases expression
  • fru-2,6-BP stimulates PFK-1??
• PFK-2: fru-6-P → fur-2,6-BP

splitting stage? splitting stage?