Glucagon & Insulin

Question 1

Primary effect of …. and …. is to prevent fasting hypoglycemia and promote liberation of free fatty acid

Answer 1

1. glucagon

2. epinephrine

Question 2

Glucagon secretion

Answer 2

1. From pancreatic alpha cells
2. Stimulated by low glucose and increased epinephrine
3. Inhibited by high blood glucose and insulin

Question 3

Exercise or stress state

Answer 3

Epinephrine

• stimulates glycogenolysis in muscle and liver
• release free fatty acids of adipose tissue

Question 4

Receptor associated with glucagon and epinephrine

Answer 4

G proteins coupled receptors

Question 5

Physiology of Glucagon and epinephrine during exercise/stress

Answer 5

1. Activation adenylate cyclase –> increase cAMP –> increase protein kinase A
2. Activation energy release
   * glycogen phosphorylase
   * hormone sensitive lipase
3. Inactivation storage
   * Glycogen synthase
   * Fatty acid synthesis

Question 6

How liver preferentially takes up glucose in early post prandial period?

Answer 6

1. nutrient-rich blood flow and insulin first goes to liver from hepatic portal vein
2. glucokinase metabolizes large amount glucose into G6P
3. Hexokinase inhibited by G6P

Question 7

Muscle metabolism fed state

Answer 7

1. increase glucose uptake by GLUT 4, phosphorylation by hexokinase and activation glycogen synthase
2. increase aa uptake and protein synthesis => storage for energy source and muscle growth
3. Decrease uptake fat due to reduction in skeletal muscle LPL caused by increased insulin

Question 8

Brain metabolism fed state

Answer 8

1. Brain fuel: glucose (sometimes ketones)
2. Not insulin sensitive GLUT => need stable concentration of glucose in bloodstream
3. Aerobic metabolism => need Oxygen!!

Question 9

Adipose tissue metabolism fed state

Answer 9

1. Hormone sensitive lipase INACTIVE => lipolysis low
2. De novo lipogenesis in adipose tissue
3. Lipoprotein lipase increase uptake dietary fat to adipose tissue

Question 10

Liver metabolism fasting

Answer 10

1. Glycogen degradation: glucagon stimulates glycogen phosphorylase and inhibits glycogen synthase
2. 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
3. increase G-6-phosphatase => release glucose from liver to blood

Question 11

Muscle metabolism fasting

Answer 11

1. Degradation of muscle protein => aa for gluconeogenesis in liver
2. increased skeletal muscle LPL and increased uptake VLDL triglyceride as source for muscl
3. Glycogen degradation provides glucose as fuel for muscle
4. Lactate generated goes to liver => Cori cycle for gluconeogensis

Question 12

Brain metabolism fasting

Answer 12

1. continues using glucose as source at the beginning

2. Liver supplies glucose to blood stream through breaking down glycogen etc…

Question 13

Liver metabolism starvation

Answer 13

1. aa from muscle protein decrease => gluconeogenesis in liver decrease
2. Lypolysis in adipose tissue release glycerol
   glycerol -> glycerol 3P -> DHAP -> glucose (in liver)
3. Fatty acid (from adipose) oxidation provides energy for gluconeogenesis.
4. Ketoacidosis = hallmark of starvation.
5. Fruity odor = not metabolized acetone

Question 14

Muscle metabolism starvation

Answer 14

1. Decrease degradation muscle protein
2. Free fatty acid, ketone and TGs = energy source
3. Starvation persists, muscle relies on free fatty acid, saving ketone for brain

Question 15

Brain metabolism starvation

Answer 15

1. Using ketone, saving glucose for RBC

2. Decrease glucose need => decrease hepatic gluconeogensis => spares muscle protein degradation