Transcript Glucose Metabolism: Generating Energy in Life and Disease

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
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The mitochondria: TCA cycle and OXPHOS:ETC
IDHx and SDHx mutations in human cancer
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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”
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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