Glucose Metabolism

Question 1

Liver vs dietary carbs

Answer 1

Liver is more important source of blood glucose than dietary carbs because of glycogenolysis (fasting) and gluconeogenesis (starved)

Question 2

Increase in blood glucose?

Answer 2

insulin release –> increases

• glycogen synthesis
• FA synthesis
• TAG synthesis
• liver glycolysis

Question 3

Decrease in blood glucose?

Answer 3

glucagon release –> increases

• glycogenolysis
• gluconeogenesis
• lipolysis
• DECREASES liver glycolysis

Question 4

Hormones that oppose insulin?

Answer 4

Glucagon, catecholamines, cortisol, growth hormone

Question 5

How is insulin release from beta-cells?

Answer 5

glucose enters through GLUT 2 –> glucokinase converts it to Glucose-phosphate –> pyruvate –> TCA cycle –> makes ATP –> ATP inhibits K channels –> depolarization of cell –> opens VG Ca channels –> Ca enters cell –> mediates fusion of insulin vesicles

Question 6

Maturity Onset Diabetes of Young

Answer 6

Type 2 diabetes -> autosomal dominant inheritance

- mutation in glucokinase –> no insulin release

Question 7

Insulin signaling promoting glucose storage

Answer 7

Insulin binds receptor -> PI-3kinase makes PI-3,4,5-trisphosphate –> recruits PDK1 and PKB to plasma membrane –> PDK1 phosphorylates PKB (Akt) –> PKB (Akt) phosphorylates intracellular targets

Question 8

PKB (Akt) intracellular targets?

Answer 8

inhibits glycogen synthase kinase-3 = inhibiting the inhibitor
activates protein-phosphatase 1 -> activates glycogen synthase
*PKB (Akt) blocks FOX01 –> this is a transcription factor for key gluconeogenesis enzymes (G6Pase, PEPCK)

Question 9

Glucagon signaling

Answer 9

glucagon binds GPCR -> activates PKA through cAMP –> PKA phosphorylates CREB –> activates PGC1a (transciptional co-activator) –> PEPCK, G6Pase

Question 10

Glucose-6-phosphate regulation of gluconeogenesis

Answer 10

G6Pase removes the P turning G6P into glucose so it can exit through GLUT 2

Question 11

PEPCK regulation of gluconeogenesis

Answer 11

converts oxaloacetate into phosphoenolpyruvate

- important with lactate and alanine

Question 12

Hepatic gluconeogenesis

Answer 12

PKA phosphorylates PFK-2 (PFK/FBPase 1)
- PFK/FBPase 1 is bifunctional –> phosphorylates F6P into F2,6BP (as well as reverse reaction)
Phosphorylation of PFK-2 inhibits kinase activity and activates phosphatase activity –> decreasing F2,6BP pool –>prevents glycolysis

Question 13

Type 1 Diabetes

Answer 13

lack of insulin –> no storage pathways activated

Question 14

Type 2 Diabetes

Answer 14

reduced insulin or insulin resistance –> storage pathways reduced

Question 15

Pathway overactive in diabetes

Answer 15

TORC2 -> PGC1a expression -> gluconeogenesis

- inhibited by Metformin

Question 16

Metformin

Answer 16

activates LKB1 -> phosphorylates AMPK –> phosphorylates TORC2 in cytoplasm -> no localization to nucleus -> no gluconeogenesis
- also effects glucagon by increasing intracellular AMP which decreases cAMP levels –> no glucagon signaling

Question 17

Mitochondria Uncouplers

Answer 17

dissipate the proton gradients without generating ATP in the mitochondria

• some natural (during cold –> induce shivering)
• DNP -> explosive

Question 18

CRMP

Answer 18

slow release modified form of DNP that doesn’t increase temp but increase fat oxidation, resulting in tissue utilization of glucose

Question 19

Testosterone effects on glucose metabolism

Answer 19

testosterone enhances insulin’s effects

• adipose tissure increases aromatase which augments conversion of testosterone to estradiol
• less testosterone leads to increased LPL and increase in adiposity

Question 20

Spermatogenesis and metabolism of glucose

Answer 20

Sertoli cells are glycolytic –> ferment glucose to lactate

• lactate is exported by MCT4
• taken up by spermatocytes by mCT2
• spermatocytes oxidize it