Question 12

College Answer

A definition of normal glucose levels was expected, mentioning how it is regulated despite variable intake. Most answers incorporated the roles of insulin/glucagon and the glucostat function of the liver. Sufficient detail regarding the mechanism of insulin release was often lacking. Extra marks were awarded for description of the role of the satiety centre in the hypothalamus, glucokinase and processes in fasting and starvation that maintain blood glucose levels.

Marks were not awarded for describing effects of insulin and glucagon unrelated to glucose control.

Discussion

• Normal blood glucose concentration
  • Normal BSL is on average 5 mmol/L during the fasting state.
  • It increases to no more than 9-10 mmol/L following a meal
  • There is a balance between tissue utilisation, release from stores, and production from dietary carbohydrates and gluconeogenesis
• Glucose sources in the post-absorptive state
  • Release from storage:
    • glycogen and fat in the liver,
    • glycogen in skeletal muscle
    • fat in adipose tissue
  • De novo synthesis:
    • Gluconeogenesis by the liver (80%) and kidney (20%)
• Glucose sensing
  • Mainly by pancreatic islet β-cells and α-cells
  • The molecular mechanism involves glucokinase, which has an affinity for glucose concentrations higher than 3-4 mmol/L
  • Glucokinase activity leads to the production of ATP and DAG
  • ATP inhibits ATP-sensitive potassium channels, depolarising the β-cell membrane and producing insulin release ( or suppressing glucagon release)
  • Minor role is played by hypothalamus and midbrain, which regulate satiety and the autonomic responses to hyper and hypoglycaemia
• Response to increased blood glucose
  • Glucagon release is suppressed
  • Insulin release is directly stimulated (biphasic pattern)
  • Insulin produces effects which promote the storage, and inhibit the release, of glucose:
    • Reduced gluconeogenesis, glycogenolysis, free fatty acid oxidation and ketone production by the liver
    • Increased glycogen synthesis and increased VLDL synthesis
    • Increased glucose uptake by insulin-sensitive tissues which express GLUT4 glucose transport channels (skeletal muscle and adipose tissue)
• Response to decreased blood glucose:
  • Insulin release is suppressed, and glucagon release is stimulated
  • Glucagon stimulates glucose mobilisation:
    • Hepatic glycogenolysis increases, liberating stored glucose
    • Hepatic and renal gluconeogenesis is stimulated
  • Glucagon inhibits the transfer of glucose into storage forms:
    • Glucagon inhibits glycolysis and hepatic glycogen synthesis
    • Glucagon also inhibits the synthesis of VLDLs and triglycerides, and stimulates the beta-oxidation of fatty acids in the liver, which promotes ketogenesis.

Gerich, John E. "Physiology of glucose homeostasis." Diabetes, Obesity and Metabolism 2.6 (2000): 345-350.

Herman, Mark A., and Barbara B. Kahn. "Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony." The Journal of clinical investigation 116.7 (2006): 1767-1775.

Niijima, Akira. "Neural mechanisms in the control of blood glucose concentration." The Journal of nutrition 119.6 (1989): 833-840.