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Transcript
Glucose Metabolism: Generating Energy in Life and Disease Hans Widlund - BWH © 2012 Why does glucose matter to us? - Energy (ATP generation) - Building block (carbon source) Hans Widlund - BWH © 2012 Where does your glucose come from? Hans Widlund - BWH © 2012 What is UP and DOWN with blood glucose? Diabetes-type 1: no beta-islet cells = no insulin (autoimmune disease) Diabetes-type 2: produce insulin but not enough to reduce blood glucose (preceded by insulin-resistance) (lifestyle + genetic modifiers) No glucose! Hans Widlund - BWH © 2012 Insulin: signaling to glucose uptake AND/OR storage (as glycogen) storage lipids energy Hans Widlund - BWH © 2012 Insulin: signaling to glucose uptake AND/OR storage (as glycogen) GSK3: glycogen synthase kinase 3 acts to inactivate GS Hans Widlund - BWH © 2012 Acetyl-CoA: the cellular currency of energy derived from food Just barely enough Caloric restriction: longevity Too much Caloric overload: obesity….. Hans Widlund - BWH © 2012 The making of Acetyl-CoA Lipid Glycolysis Glycolysis Glucose Pyruvate Fatty Acid Acetyl-CoA The Citric Acid (TCA) cycle (Krebs cycle) ATP production Hans Widlund - BWH © 2012 The making of Acetyl-CoA (2) Pentose Pathway (oxidative stress response & nucleotides) ATP PFK1 (phosphofructokinase): activated by AMP (low energy state) lipids PEP Sialic acid PK (pyruvate kinase): PKM1/2 PEP F1,6P2 Pyruvate + ATP Acetyl-CoA Pyruvate + ATP MUSCLE/BRAIN CANCER CELLS Hans Widlund - BWH © 2012 The mitochondria: TCA cycle and OXPHOS:ETC IDHx and SDHx mutations in human cancer Hans Widlund - BWH © 2012 Aging of the cell through the mitochondria (a theory) Hans Widlund - BWH © 2012 Renew the mitochondria through exercise and/or fasting (or wine) Autophagy “Mitophagy” Hans Widlund - BWH © 2012 WELLNESS: Exercise well and eat, drink with modesty State-of-the-Department gift! -Measure # steps -Calories burned -Fat loss Can be PC-connected to monitor data Burn your calories, reduce your fat (blood glucose), live longer and healthier Hans Widlund - BWH © 2012