Question 1

College Answer

It was expected answers would include a comment this would transiently increase the blood glucose and result in the stimulation of insulin production. Some detail was then required on the mechanism by which insulin production is increased and time frames over which this occurred, as well as mechanism by which glucose passes through to the urine. Other important points expected were the fate of glucose, once taken up by the cells, the inhibitory effects (and mechanisms) of insulin (ie inhibits glycogenolysis, triglyceride and protein breakdown, etc). A description of the physiological consequences of increased insulin production was required. This question has been asked before, in it’s current form. The pass rate on this occasion was higher. Candidates who did poorly did so due to a lack of detail and understanding of the topic. 

Discussion

Judging from the examiner comments, something like the following was expected:

• Immediate biochemical effects:
  • BSL would increase ( up to 13-15 mmol/L after 5 minutes)
  • This would be transient (~ 30 minutes)
  • Serum osmolality would increase (below osmoreceptor threshold)
  • Blood volume would increase (slightly)
  • Osmotic effects of the excess glucose in the renal tubule fluid produce an osmotic diuresis and glycosuria
• Glucose sensing by pancreatic β-cells and α-cells
  • Glucose diffusion and conversion by glucokinase would result in ATP generation which influences ATP-sensitive potassium channels
  • This depolarises the cells and leads to increased insulin degranulation and decreased glucagon degranulation
• Insulin is released in a biphasic pattern
  • Insulin binds to its receptors (tyrosine kinase intracellular domain)
  • Multiple metabolic 
• Immediate effects of insulin on the liver:
  • Reduced gluconeogenesis, urea synthesis, glycogenolysis, free fatty acid oxidation and ketone production
  • Increased glycogen synthesis and VLDL synthesis
  • This decreases glucose release by the liver, and increases glucose uptake
• Effects of insulin on insulin-sensitive tissues:
  • On binding of insulin to its receptor in these tissues, GLUT4 transport proteins are translocated to the surface, increasing the permeability of the cell membrane to glucose
  • Effect of insulin on the skeletal muscle
    • Increased glycogen synthesis
    • Increased protein synthesis and decreased protein catabolism
  • Effect of insulin on adipose tissue
    • Increased synthesis of triglycerides and decreased lipolysis
    • Increased lipoprotein lipase activity
    • Increased uptake of free fatty acids

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.

Regittnig, Werner, et al. "Assessment of transcapillary glucose exchange in human skeletal muscle and adipose tissue." American Journal of Physiology-Endocrinology and Metabolism 285.2 (2003): E241-E251.

Balentine, Jerry R., et al. "Effect of 50 milliliters of 50% dextrose in water administration on the blood sugar of euglycemic volunteers." Academic emergency medicine 5.7 (1998): 691-694.