Glucagon & Insulin Flashcards
Primary effect of …. and …. is to prevent fasting hypoglycemia and promote liberation of free fatty acid
- glucagon
2. epinephrine
Glucagon secretion
- From pancreatic alpha cells
- Stimulated by low glucose and increased epinephrine
- Inhibited by high blood glucose and insulin
Exercise or stress state
Epinephrine
- stimulates glycogenolysis in muscle and liver
- release free fatty acids of adipose tissue
Receptor associated with glucagon and epinephrine
G proteins coupled receptors
Physiology of Glucagon and epinephrine during exercise/stress
- Activation adenylate cyclase –> increase cAMP –> increase protein kinase A
- Activation energy release
* glycogen phosphorylase
* hormone sensitive lipase - Inactivation storage
* Glycogen synthase
* Fatty acid synthesis
How liver preferentially takes up glucose in early post prandial period?
- nutrient-rich blood flow and insulin first goes to liver from hepatic portal vein
- glucokinase metabolizes large amount glucose into G6P
- Hexokinase inhibited by G6P
Muscle metabolism fed state
- increase glucose uptake by GLUT 4, phosphorylation by hexokinase and activation glycogen synthase
- increase aa uptake and protein synthesis => storage for energy source and muscle growth
- Decrease uptake fat due to reduction in skeletal muscle LPL caused by increased insulin
Brain metabolism fed state
- Brain fuel: glucose (sometimes ketones)
- Not insulin sensitive GLUT => need stable concentration of glucose in bloodstream
- Aerobic metabolism => need Oxygen!!
Adipose tissue metabolism fed state
- Hormone sensitive lipase INACTIVE => lipolysis low
- De novo lipogenesis in adipose tissue
- Lipoprotein lipase increase uptake dietary fat to adipose tissue
Liver metabolism fasting
- Glycogen degradation: glucagon stimulates glycogen phosphorylase and inhibits glycogen synthase
- Gluconeogenesis:
* reduction F-2,6-BP => activation of of F-1,6-BP and decrease PFK1 activity
* Inactivation pyruvate kinase (through protein kinase A)
* Increase lyposis => increase fatty acid => increase acetyl CoA => MAKING gluose - increase G-6-phosphatase => release glucose from liver to blood
Muscle metabolism fasting
- Degradation of muscle protein => aa for gluconeogenesis in liver
- increased skeletal muscle LPL and increased uptake VLDL triglyceride as source for muscl
- Glycogen degradation provides glucose as fuel for muscle
- Lactate generated goes to liver => Cori cycle for gluconeogensis
Brain metabolism fasting
- continues using glucose as source at the beginning
2. Liver supplies glucose to blood stream through breaking down glycogen etc…
Liver metabolism starvation
- aa from muscle protein decrease => gluconeogenesis in liver decrease
- Lypolysis in adipose tissue release glycerol
glycerol -> glycerol 3P -> DHAP -> glucose (in liver) - Fatty acid (from adipose) oxidation provides energy for gluconeogenesis.
- Ketoacidosis = hallmark of starvation.
- Fruity odor = not metabolized acetone
Muscle metabolism starvation
- Decrease degradation muscle protein
- Free fatty acid, ketone and TGs = energy source
- Starvation persists, muscle relies on free fatty acid, saving ketone for brain
Brain metabolism starvation
- Using ketone, saving glucose for RBC
2. Decrease glucose need => decrease hepatic gluconeogensis => spares muscle protein degradation
