Artificial Pancreas - Background in Endocrine Physiology

Background in Endocrine Physiology

The pancreas produces three hormones that are important to glycemic control:

• insulin, which lowers blood glucose;
• amylin, which slows digestion and slows the rate of glucose entering the bloodstream, and temporarily suppresses release of glucagon;
• and glucagon, which raises the blood glucose.

Upon digestion of carbohydrates, glucose levels in the blood will begin to rise. As the blood and glucose flow into the pancreas, insulin and amylin are cosecreted by the pancreatic beta cells directly into the bloodstream in response to elevated blood glucose levels. In the presence of glucose these insulin responses are almost exclusively delivered in boluses every 4 to 6 minutes. Insulin causes blood glucose to be removed from the bloodstream and stored in the liver and muscle cells. As the blood sugar goes higher, additional insulin will bring the blood sugar back down in a classic negative feedback loop. As insulin is released from the beta cells, amylin is also released into the bloodstream. Amylin slows gastric emptying, and also inhibits the release of glucagon from the pancreatic alpha cells. The effect of amylin is to spread out the blood glucose peak after eating, reducing the quantity of insulin needed. As the blood sugar level comes back toward normal, the beta cells will stop spurting insulin and amylin. As the glucose level approaches a low mark, the pancreatic alpha cells will release glucagon directly into the bloodstream. Glucagon causes the liver to release stored glucose back into the bloodstream. Increased glucagon will increase blood glucose levels to produce a positive error in the negative feedback loop. Together, the three endocrine hormones work as a system to maintain the blood glucose level between high and low boundaries. By delivering the insulin in boluses as presented by a non-diabetic pancreas, the goal of an artificial pancreas can be achieved.

When the beta cell produces insulin from proinsulin, a connecting peptide (or C-peptide) is also manufactured and released into the bloodstream. Absence of C-peptide in the blood indicates that insulin has not been released from the pancreas, and this fact confirms the diagnosis of diabetes type 1. C-peptide was believed to be only a by-product of natural insulin production, however recent studies suggest that C-peptide exerts beneficial therapeutic effects on diabetic nociceptive neuropathy.

Ideally, to replicate the natural function of the pancreas as closely as possible, an artificial pancreas might someday replace all of the beneficial endocrine functions lost, including the delivery of insulin, amylin, glucagon, and C-peptide.