Hormones

The pancreas folds under the stomach, secretes the hormones insulin, glucagon, and somatostatin. About 70% of the pancreatic hormone-secreting cells are called beta cells and secrete insulin; another 22%, or so, are called alpha cells and secrete glucagon. The remaining gamma cells secrete somatostatin, also known as growth hormone inhibiting hormone (GHIH). The alpha, beta, and gamma cells comprise the islets of Langerhans which are scattered throughout the pancreas.

Insulin and glucagon have reciprocal roles. Insulin promotes the storage of glucose, fatty acids, and amino acids, whereas, glucagon stimulates mobilization of these constituents from storage into the blood. Both are relatively short polypeptides. Insulin release is triggered by high blood glucose levels. It lowers blood sugar levels by binding a cell surface receptor and accelerating glucose transport into the cell where glucose is converted into glycogen. Insulin also inhibits the release of glucose by the liver in order to keep blood levels down. Increased blood levels of GH and ACTH also stimulate insulin secretion. Not all cells require insulin to store glucose, however. Brain, liver, kidney, intestinal, epithelium, and the pancreatic islets can take up glucose independently of insulin. Insulin excess can cause hypoglycemia leading to convulsions or coma, and insufficient levels of insulin can cause diabetes mellitus which can be fatal if left untreated. Diabetes mellitus is the most common endocrine disorder.

Glucagon secretion is stimulated by decreased blood glucose levels, infection, cortisol, exercise, and large protein meals. GHIH, glucose, and insulin inhibit its secretion. Protein taken in through the digestive tract has more of a stimulatory effect on glucagon than does injected protein. Glucagon stimulates glycogen breakdown in the liver, inhibits glycogen synthesis, and facilitates glucose release into the blood. Excess glucagon can result from tumors of the pancreatic alpha cells; and a mild diabetes seems to result. Some cases of uncontrolled diabetes are also characterized by high glucagon levels suggesting that low blood insulin levels are not always the only cause in some diabetes cases.

It was the study of glucagon and its action by Sutherland in 1961 that led to the concept of the second messenger system. Glucagon activates the intracellular molecule cyclic AMP, cAMP. Since this discovery, a number of other molecules have been found which modulate cellular activity via this second messenger.