Feeding and Fasting: integration of glucose and fat metabolism Flashcards
Key hormones in short term regulation of blood glucose
insulin (reduce blood sugar – hypoglycemic effect)
glucagon (along w/ epi, GH, cortisol act to increase blood sugar– hyperglycemic effect)
fat metab and rising insulin/falling catecholamines
-inhibition of lipolysis thus reducing fatty acid oxidation and facilitating fatty acid synthesis
very low insulin and high counter regulatory hormones and fat metab
-fatty acids enter ketogenesis pathway (instead of being oxidized to CO2 and water)
When are counter regulatory hormones released?
When glucose FALLS
What fuel do muscles prefer?
fatty acids for fuel preferred, but can consume glucose when insulin rises.
Where are effects of insulin most pronounced? results?
- liver, muscle, and adipose tissue
- effect of insulin is to promote storage of excess glucose as glycogen in liver and muscle and as triglycerides in adipose tissue
insulin release is timulated by:
- increase in blood glucose
- increase in indiv aa (argninie, leucine)
- facilitated by gut hormone GLP-1
Glucagon release stimulated by
-low glucose and increased epi
inhibited by high glucose and insulin
During fasting, primary actor?
- glucagon acts primarily on liver
- promotes glycogenolyis and gluconeogenesis
During exercise/stress: action of epi
- stimulates glycogenolysis in muscle and liver and release of FFA by adipose tissue thru hormone sensitive lipase
- hormone binding–> cAMP–> PKA–> glycogen phosphorylase and hormone sensitive lipase activation (and inactivation of glycogen synthase; acetyl coA carboxylase in fatty acid synthesis)
Fed state: 1-3 hours after ingestion of meal
- high insulin/glucagon ratio
- modest rise in blood glucose
What organ preferentially takes up glucose in post-prandial period?
- liver (using glucokinase to convert glucose from portal v to G6P)
- elevated G6P in liver along with high insulin levels stimulates glycogen synthase
Enzymes favored by high insulin/glucagon ratio
glycogen synthase (active form is dephosphorylated)
pyruvate dehydrogenase (provides lots of acetyl CoA for FFA synthesis, facilitated by activation of acetyl CoA carboxylase (rate limiting step) (Also need NADPH from PPP for fatty acid synthesis by fatty acid synthase)
Muscle metabolism in fed state
high insulin/glucagon ratio:
- increased glucose uptake (Glut-4)
- glucose to G6P by hexokinase
- activation of glycogen synthase
- glucose is primary fuel for muscle in fed state
- increased aa uptake and protein synthesis–> storage of carbon skeletons
- NOT favored: uptake of fat in chylomicrons due to reduction in skel muscle LPL caused by increased insulin levels.
Brain metabolism in fed state
- glucose is EXCLUSIVE fuel for brain tissue (except in extreme starvation: ketone bodies)
- use of insulin dependent glucose transporters (Glut-1, Glut-3)
- brain relies on aerobic metab of glucose