Researchers have identified two distinct phases of insulin secretion by the pancreas that occur when study subjects are given an intravenous glucose injection. The first phase occurs within the first few minutes after the glucose injection, when the blood glucose level abruptly rises. That phase of insulin release, which subsides after about 10–15 minutes, is thought to involve the release of insulin already stored within the beta cells. The first phase is followed by a second phase of insulin release, which is more prolonged.
Researchers think that similar phases occur in response to carbohydrate that is ingested, rather than injected. They speculate that the early stage of insulin secretion is very important for proper glucose metabolism, and that when it goes awry, it may set the stage for impaired glucose tolerance and Type 2 diabetes. When the early-stage insulin secretion is diminished, blood glucose levels tend to rise significantly right after meals. The pancreas compensates for this rise by increasing the second-phase insulin secretion, which eventually brings blood glucose levels back to normal. However, these high levels of glucose and insulin in the bloodstream may damage the beta cells and further impair their ability to function. The chronically high levels of insulin can also play a role in increased insulin resistance, contributing to chronic high blood glucose and full-blown Type 2 diabetes.
Different types of medicines for Type 2 diabetes lower blood glucose levels in different ways. Sulfonylureas such as glimepiride (brand name Amaryl), glyburide (Diabeta, Glynase, Micronase), and glipizide (Glucotrol, Glucotrol XL) increase both first-phase and second-phase insulin secretion. The drugs repaglinide (Prandin) and nateglinide (Starlix), which stimulate the pancreas to release more insulin just after meals, and the injectable drugs exenatide (Byetta, Bydureon) and liraglutide (Victoza) have a greater effect on early-stage insulin secretion. Some researchers speculate that intensively treating the early-stage insulin secretion may slow the progression of Type 2 diabetes early in the course of the disease.