Glucose Metabolism [skildum] Flashcards
Decreased blood glu triggers what to be released?
What functions does this carry out?
Glucagon releases:
- increased glycogenolysis
- increased GNeo
- increased lips lysis
- decreased liver glycolysis
In fasting, How long can hepatic glycogenolysis sustain us (our glu supply)?
About 24 hours
Then we completely switch to GNeo (it’s been slowly increasing over those 24 hrs)
Increased blood glu triggers what to be released?
What functions does it carry out?
Insulin release:
- increased glycogen synthesis
- increased FA synth
- increased TG synth
- increased liver glycolysis
What substances oppose the actions of insulin? (Insulin decreases glu production & increases glu use)
Glucagon
Catecholamines
Cortisol
GH
In the fasting state, what does glucagon binding in the liver potentials?
Glucagon binds➡️PKA ➡️ de phosphorylation of CRTC2 & FoxO1 ➡️ CRTC2, FoxO1 & CREB relocate to nucleus➡️ INCREASE TRANSCRIPTION of PEPCK & G6Pase ➡️
Increases hepatic GNeo
In the fed state, What does insulin binding in the liver potentiate?
What R does insulin bind?
Insulin binds a tyrosine kinase R➡️ Akt (aka PKB)➡️ phosphorylation of FOxO1 & CRTC2 (they can’t move into the nucleus)➡️ decrease levels of PEPCK & G6Pase transcription
DECREASED GNeo!!
Describe how insulin is secreted from beta cells of the pancreas?
- Glu enters cell via GLUT2
- Gets phosphorylated by glucokinase ➡️TCA cycle➡️ATP
- ATP inhibits K+ channel
- Cell depolarizes and VG Ca+ channel opens
- Ca influx causes vehicle to release insulin
In Maturity Onset Diabetes of the Young type 2 (MODY2) what mutation is present?
Glucokinase is mutated (autosomal dominant)
-inhibits glucose triggering Insulin release from beta cells
What does active PKB/Akt trigger?
Inhibits glycogen synthase3 (normally inhibits glycogen synthase)
& blocks transcription factor FoxO1 by phosphorylating it
Activates protein phosphatSe1 which activates glycogen synthase
ULTIMATELY: promotes glycogen synthase (glu uptake)
What does metformin target in the cell? MOA?
Metformin activates LKB
- LKB activates (phosphorylates) AMPK
- AMPK phosphorylates TORC2 and thus keeps it out of the nucleus
Keeping TORC2 out prevents it from acting with CREB to increase PGC1a expression and thus decrease GNEO (decreases blood glu!)
What is a new potential target for diabetes medication?
How does it work?
Mitochondrial uncoupling!!!!
- dinitrophenol (UCP2)
- allows controlled proton leak back into mito➡️reduces membrane potential (potentiate insulin release!!!)
How does testosterone influence glucose metabolism?
Testosterone enhances insulins effect on glu metabolism!!
- Increases GLUT4 expression/translocation to membrane on cells
- Increases glycolysis enzyme expression in cells (G6PDH, PFK etc)
- Increases oxidative phosphorylation
What 2 substances released from adipose tissue can have an effect on testosterone/androgen levels?
AROMATASE: converts test ➡️ estradiol, estradiol makes kisspeptin which inhibits hypo/pit/teste axis ➡️ decreased testosterone
LEPTIN: inhibits gonadotropins from acting on leydig cells of testes➡️ decreased androgen
What is special about serotonin cells and their relationship to spermatocytes?
Sertolis are glycolysis & ferment glu ➡️lactate
- Lactate is then exported thru MCT4 & taken up by spermatocytes via MCT2
- Spermatocytes then oxidize lactate (for fuel)
Which cells in the female are similar to the sertoli/spermatocytes relationship?
Cumulus cells take up glu ➡️ (glycolysis & fermenting) ➡️ provide substrate for oocytes oxidative phosphorylation
