Wk1 Glucose Metabolism

Question 1

Duration of ingested glucose oxidation for fuel after a meal:

Answer 1

~ 4 hrs – decreases rapidly then switches to glycogenolysis in liver

slides 4-5

Question 2

Four main processes stimulated by insulin:

Answer 2

1. glycogen synthesis
2. FA synthesis
3. TG synthesis
4. Liver glycolysis

Question 3

3 main processes stimulated by glucagon:

Answer 3

1. glycogenolysis
2. gluconeogenesis
3. lipolysis

Question 4

Four substances that oppose insulin:

Answer 4

1. Glucagon
2. catecholamines
3. cortisol
4. Growth hormone

**all stimulate liver to produce glucose

Question 5

Pathway for insulin release from pancreatic beta cells:

Answer 5

glucose –> GLUT 2 into cell –> TCA cycle –> ATP –> inhibits K+ channel –> depolarizes cell –> increased intracellular Ca++ –> Ca mediated fusion of insulin containing vesicles with plasma membrane

**slide 10

Question 6

Deficiency in glucokinase in pancreatic beta cells:

Answer 6

MODY2

maturity onset diabetes of the young type 2

Question 7

Insulin receptor type in tissue cells:

Answer 7

tyrosine kinase –> PI-3,4,5-trisP –> PDK 1 phosphorylates PK B –> active PK B phosphorylates intracellular targets to modulate metabolism

Question 8

PK B effect on glycogen synthase:

Answer 8

activation via inhibition of glycogen synthase kinase-3

and

activation of protein phosphatase-1

Question 9

Two key gluconeogenic enzymes:

What transcrition factor regulates them?

Answer 9

G-6-P

PEP-CK

FOX01

Question 10

PKB (Akt) effect on FOX01:

Answer 10

inhibits expression by phosphorylating it

• *so insulin inhibits gluconeogenesis
• which makes sense because there is glucose available in the blood already

Question 11

glucagon pathway to gluconeogenesis in fasted stated:

Answer 11

GPCR –>cAMP –> PKA –> CREB –> PGC1a –> PEPCK and G6P

Question 12

Recap of insulin vs glucagon on ….

Answer 12

slide 18

Question 13

Fruc 2,6 BP and Fruc 6-P

Which inhibits and which activates PFK?

Answer 13

F2,6 – activates (glucose abundant)

F6P – inhibits (glucose scarce)

Question 14

glucagon effect on Fruc 2,6 BP:

Answer 14

inhibits –> inhibiting glycolysis and promoting gluconeogenesis

Question 15

Other than decreased glucose uptake, what two thing happen with insulin deficiency?

Answer 15

glucagon in excess with lack inhibition by insulin causing:

1. increased protein catabolism –> increased gluconeogenisis –> even higher blood sugar
2. increased lipolysis –> increased ketogenesis –> can lead to ketoacidosis

Question 16

DM1 vs DM2?

Answer 16

DM1: increased TAG, ketone bodies, FAs, Glucose

DM2: increased TAG and Glucose only

**slide 25

Question 17

Metformin MOA:

Answer 17

activates LKB1

LKB1 phosphorylates (activates) AMPK

AMPK phosphorylates TORC2 (preventing it from transcribing gluconeogenic genes in nucleus)

Question 18

Good luck

Answer 18

this shit is hard