Glucose Metabolism Flashcards
Liver vs dietary carbs
Liver is more important source of blood glucose than dietary carbs because of glycogenolysis (fasting) and gluconeogenesis (starved)
Increase in blood glucose?
insulin release –> increases
- glycogen synthesis
- FA synthesis
- TAG synthesis
- liver glycolysis
Decrease in blood glucose?
glucagon release –> increases
- glycogenolysis
- gluconeogenesis
- lipolysis
- DECREASES liver glycolysis
Hormones that oppose insulin?
Glucagon, catecholamines, cortisol, growth hormone
How is insulin release from beta-cells?
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
Maturity Onset Diabetes of Young
Type 2 diabetes -> autosomal dominant inheritance
- mutation in glucokinase –> no insulin release
Insulin signaling promoting glucose storage
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
PKB (Akt) intracellular targets?
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)
Glucagon signaling
glucagon binds GPCR -> activates PKA through cAMP –> PKA phosphorylates CREB –> activates PGC1a (transciptional co-activator) –> PEPCK, G6Pase
Glucose-6-phosphate regulation of gluconeogenesis
G6Pase removes the P turning G6P into glucose so it can exit through GLUT 2
PEPCK regulation of gluconeogenesis
converts oxaloacetate into phosphoenolpyruvate
- important with lactate and alanine
Hepatic gluconeogenesis
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
Type 1 Diabetes
lack of insulin –> no storage pathways activated
Type 2 Diabetes
reduced insulin or insulin resistance –> storage pathways reduced
Pathway overactive in diabetes
TORC2 -> PGC1a expression -> gluconeogenesis
- inhibited by Metformin
Metformin
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
Mitochondria Uncouplers
dissipate the proton gradients without generating ATP in the mitochondria
- some natural (during cold –> induce shivering)
- DNP -> explosive
CRMP
slow release modified form of DNP that doesn’t increase temp but increase fat oxidation, resulting in tissue utilization of glucose
Testosterone effects on glucose metabolism
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
Spermatogenesis and metabolism of glucose
Sertoli cells are glycolytic –> ferment glucose to lactate
- lactate is exported by MCT4
- taken up by spermatocytes by mCT2
- spermatocytes oxidize it
