Glucose Metabolism:

Generating Energy in Life and Disease

Hans Widlund - BWH © 2012

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?

No 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)

Hans Widlund - BWH © 2012

Insulin: signaling to glucose uptake AND/OR storage (as glycogen)

storage

energylipids

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

Too muchJust barely enough

Caloric restriction: longevityCaloric overload: obesity…..

Hans Widlund - BWH © 2012

The making of Acetyl-CoA

Glucose Lipid

Pyruvate Fatty Acid

Acetyl-CoA

ATP production

Gly

coly

sis

-ox

idat

ion

The Citric Acid (TCA) cycle(Krebs cycle)

Gly

coly

sis

Hans Widlund - BWH © 2012

PFK1 (phosphofructokinase): activated by AMP (low energy state)ATP

Acetyl-CoA

The making of Acetyl-CoA (2)

PK (pyruvate kinase): PKM1/2

Pyruvate + ATPPyruvate + ATP

PEP PEP

CANCER CELLSMUSCLE/BRAIN

F1,6P2Sialic acid

PentosePathway(oxidative

stressresponse &nucleotides)

lipids

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