Feeding & Fasting

Question 1

Changes in insulin, glucagon, triglycerides, fatty acids and glucose following meal

Answer 1

• Metabolic activity shifts towards energy storage (glycogen and lipid synthesis)
  
  • 1-3 hours after meal:
    
    • High insulin:glucagon ratio
    • Elevated blood glucose (circulating absorbed dietary glucose)
  • 3-4 to 32-36 hours after meal:
    
    • Decreasing levels of absorbed nutrients in bloodstream
    • Declining insulin:glucagon ratio
    • Metabolic activity shifts to increasing reliance on glycogenolysis and gluconeogenesis.

Question 2

Liver metabolism of glucose in fed state

Answer 2

• Hepatic portal vein delivers venous blood containing absorbed nutrients and elevated levels of insulin directly to liver
• Glucokinase in liver traps this influx as G6P. Liver preferentially takes up glucose in early post-prandial period
  
  • Hexokinase is active only at high glucose concentrations but is not inhibited by G6P
• Elevated G6P in liver + high insulin levels –> increased glycogen synthase –> increased glycogen synthesis

Question 3

Liver metabolism of glucose in fasted state

Answer 3

• Glycogenolysis stimulated by:
  
  • glucagon-induced activation of glycogen phosphorylase
  • inhibition of glycogen synthase
• Gluconeogenesis stimulated via:
  
  • reduction in F2,6-BP concentration –> relieves inhibition of F-1,6-Bpase (rate limiter) –> reduces activation of PFK1
• Net result:
  
  • increased gluconeogenesis
  • decreased glycolysis
• Inactivation of pyruvate kinase (via protein kinase A) prevents futile recycling of PEP.
• G6P is present in liver but not muscle - allows glucose from glycogenolysis and gluconeogenesis to be released into blood.
  
  • G6Pase converts G6P –> glucose.

Question 4

Muscle metabolism of glucose in fed state

Answer 4

• High insulin:glucagon ratio promotes the following actions in muscle:
  
  • Increased glucose uptake by GLUT4
  • Phosphorylation of glucose by hexokinase to G6P
  • Activation of glycogen synthase –> formation of glycogen
• Glucose is primary fuel for muscle in fed state.
• Increased AA uptake & protein synthesis –> storage of carbon skeletons for use as energy source.
• Uptake of dietary fat in chylomicrons not favored (reduction in skeletal mucsle LPL due to increased insulin)

Question 5

Muscle metabolism of glucose in fasted state

Answer 5

• Degradation of muscle protein –> carbon skeletons for hepatic gluconeogenesis.
• Most AAs released from muscle protein are taken directly to liver, transaminated, converted into glucose.
• FFAs are primary fuel source for muscle during fasting. Low insulin, high counter-regulatory hormones favor increased skeletal muscle LPL as fat fuel source.
• Glycogen degradation provides glucose as fuel for muscle during short periods of exertion.
  
  • Degradation of muscle glycogen cannot contribute to blood glucose (muscle lacks G6Pase).
• Glycogen from muscle can go down glycolysis to lactate
  
  • Exported to liver to serve as gluconeogenic precursor

Question 6

Brain metabolism of glucose in fed state

Answer 6

• Glucose is exclusive fuel for brain tissue
  
  • Except in extreme starvation (ketone bodies).
• Most of brain is not insulin sensitive
  
  • Except for small population of neurons in hypothalamus (regulate food intake)
• Uptake by brain is concentration dependent
  
  • Relies on stable concentration of glucose in bloodstream
• Brain normally relies on aerobic metabolism of glucose
  
  • Hypoxia and severe hypoglycemia lead to similar symptoms
    
    • confusion, ataxia, visual disturbances

Question 7

Brain metabolism of glucose in fasted state

Answer 7

• Continues to use glucose as energy source
• Dependent on hepatic glycogenolysis and gluconeogenesis to maintain blood glucose

Question 8

Adipose tissue metabolism of glucose in fed state

Answer 8

• When insulin is high and catecholamines are low:
  
  • Lipase is not active –> rates of lipolysis are low.
• Glucose taken up by adipose tissue –> fatty acids –> triglycerides (fatty acid synthesis)
• Uptake of dietary fat contained in circulating chylomicrons facilitated by increase in adipose tissue lipoprotein lipase