14.01.2 Physiology of the Pancreas

Figure 14.1 Glucose and insulin secretion (Copyright QUT, Sheila Doggrell)

In type 2 diabetes, drugs are used to block the K⁺_ATP channel to increase the secretion of insulin. By blocking the K⁺_ATP channel, drugs mimic the effect of glucose to increase the amounts of K⁺ in the cell, and this depolarization opens the voltage-dependent Ca²⁺ channels. Ca²⁺ entry into the beta cells promotes insulin secretion.

During fasting (e.g. between meals) the levels of insulin are low. During a meal, when glucose stimulates the release of insulin, there is a rapid twofold rise in the concentration of insulin. Insulin stimulates the conversion of glucose to glycogen in the liver, the conversion of glucose to triglycerides in adipose tissue, and the conversion of amino acids to protein in muscle. Insulin inhibits the breakdown of glycogen, triglycerides and protein, including the conversion of amino acids to glucose in the liver, by the process known as gluconeogenesis. Thus, insulin is stimulating the clearance of glucose from the plasma, and inhibiting the formation of glucose, and thus, the increased levels of glucose after a meal steady decline.

The alpha cells of the pancreas produce glucagon, which is a hormone that has the opposite effects to insulin. For instance it promotes the conversion of glycogen to glucose. Under physiological conditions, insulin and glucagon are not secreted at the same time, as they would cancel each other out. Glucagon is used as a drug to treat severe hypoglycemia (unwanted effect of some anti-diabetic drugs). Thus, some of the anti-diabetic drugs not only reduce hyperglycemia to normoglycemia, but are capable of reducing normoglycemia to hypoglycemia.

Insulin is secreted from a specialized part of the pancreas known as the Islets of Langerhans. The beta cells of the islets secrete insulin. The secretion of insulin is increased by glucose, amino acids, and fatty acids. For glucose, the mechanism is that the glucose is transported into beta cells, where it is metabolized (Figure 14.1). This glucose metabolism leads to ATP formation, and ATP closes the K⁺-ATP-dependent channel. Normally, the K⁺-ATP channel is open and K⁺ moves out of the cell through this ion channel, keeping the membrane potential low. When the K⁺-ATP channel is blocked by ATP from the metabolism of glucose, the amounts of K⁺ in the cell increases, and this depolarization opens the voltage-dependent Ca²⁺ channels. Ca²⁺ entry into the beta cells promotes insulin secretion.