April 11, 2008
Other, Type 2
Question from India:
I read the following in Wikipedia: “Oscillations – Even during digestion, generally the hours following a meal, insulin release from the pancreas is not continuous, but oscillates with a period of three to six minutes, changing from generating a blood insulin concentration more than ~800 pmol/l to less than 100 pmol/l. This is thought to avoid receptor down-regulation of insulin receptors in target cells and to facilitate for the liver to extract insulin from the blood.” Furthermore, “Degradation – Once an insulin molecule has docked onto the receptor and effected its action, it may be released back into the extracellular environment or it may be degraded by the cell. Degradation normally involves endocytosis of the insulin-receptor complex followed by the action of insulin degrading enzyme. Most insulin molecules are degraded by liver cells. It has been estimated that a typical insulin molecule that is produced endogenously by the pancreatic beta cells is finally degraded about 71 minutes after its initial release into circulation.”
The above aspects are thought to be related to insulin resistance by down-regulation by more and continual insulin’s exposures. How are the above considerations maintained for giving oral hypoglycemics or injected insulin?
Answer:
It has been noted and written that oral sulfonylureas and long-acting insulin therapy can down-regulate insulin receptors. However, this happens fairly early in the progression of type 2 diabetes where endogenous insulin levels are elevated. Remember that by the time patients become hyperglycemic, they have already lost an inordinate amount of beta cell function. These medications either boost that production (sulfonylureas) or replace that production (injected insulin). So, the trade-off is probably in terms of the ability to bring the glucose levels down.
JTL
