Question 4(p.2)

College Answer

To pass this question, the candidate only needed to state the range of normal blood glucose, define hypoglycaemia then give an overview of the body's response to hypoglycaemia (control of blood glucose - sensors, integrators, effectors). Additional credit was given for a more detailed description of the various responses. Few candidates mentioned the role of the sympathetic nervous system. Much time was wasted in giving detailed descriptions of metabolic pathways to the exclusion of an overview of the body's responses.

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 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 decreased blood glucose:
  • Insulin release is suppressed, and glucagon release is stimulated by:
    • Direct effect of hypoglycaemia
    • By the removal of paracrine insulin-mediated suppression of glucagon release
    • By the sympathetic nervous system, which innervates the pancreatic islets
  • 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.

Taborsky Jr, Gerald J., and Thomas O. Mundinger. "Minireview: the role of the autonomic nervous system in mediating the glucagon response to hypoglycemia." Endocrinology 153.3 (2012): 1055-1062.