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ERG Review 2014. Eric Niederhoffer, Ph.D. SIU-SOM. What is the effect of diabetes on glycogen? What is the difference between the PFK2-F26BPase activity/regulation in the liver versus in the heart ? How is glucokinase regulated?

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ERG Review 2014

Eric Niederhoffer, Ph.D.

SIU-SOM

outline
What is the effect of diabetes on glycogen?

What is the difference between the PFK2-F26BPase activity/regulation in the liver versus in the heart?

How is glucokinase regulated?

Do insulin and glucagon play a role in regulating pyruvate kinase and pyruvate dehydrogenase kinase?

Outline
impact of diabetes on glycogen
Impact of Diabetes on Glycogen

Glycogen breakdown

Ep(ML)

Glucagon (L)

Insulin (ML)

βAR

cAMP

IR

PKA

PKA

AKT

PDK-1

PPKP

PPK

PPaP

PPb

GSK-3P

AKTP

PKA

PPKP

GSK-3

Glycogen

GS

Glycogenesis

GSPn

PPaP

UDP-Glc

PrPase1P

Glycogenolysis

G1P

PrPase1

Glc

G6P

Glycolysis

ETC

TCA

f26bpase pfk 2 regulation comparison

Glucagon

Ep

Insulin

F26BPase-PFK-2P

Liver

PKA

PrPase2A

F26BPase-PFK-2

F26BPase-PFK-2

Skeletal Muscle

F6P↑

F6P↓

F26BPase-PFK-2

Ep

Insulin

F26BPase-PFK-2

PKA

Heart

???

AKT/WISK

F26BPaseP-PFK-2

F26BPase-PFK-2 Regulation Comparison
regulation of glucokinase
Regulation of Glucokinase

GLUT2

Glucose

GLUT5

Fructose

GK

FK (KHK)

G6P

Cytosol

PGI

F6P

F1P

nucleus

GK

GK

GKRP

GKRP

AMPK

GKRP

GKRPP

regulation of pyruvate and pyruvate dehydrogenase k inase

Glucagon

Ep

also represses PFK synthesis

Insulin

Glc

G6P

F26BPase-PFK-2P

PKA

PrPase2A

F6P

F26BPase-PFK-2

F26BP

F16BP

ATP

Cit

Alanine

PEP

PKA

PKP

Pyr

PDHK

PDHP

ATP

NADH

PDHPase

Acetyl-CoA

PrPase

Regulation of Pyruvate and Pyruvate Dehydrogenase Kinase

GK

PFK-1

PK

PDH

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