The Beta Cell and First-Phase Insulin Secretion: Phases of Insulin Secretion

Phases of Insulin Secretion

In nondiabetic individuals, approximately 50% of the total daily insulin is secreted during basal periods, suppressing lipolysis, proteolysis, and glycogenolysis. The remainder of insulin secretion is postprandial. In response to a meal, there is a rapid and sizable release of preformed insulin from storage granules within the beta cell. This "first phase" of insulin secretion promotes peripheral utilization of the prandial nutrient load, suppresses hepatic glucose production, and limits postprandial glucose elevation. First-phase insulin secretion begins within 2 minutes of nutrient ingestion and continues for 10 to 15 minutes. The second phase of prandial insulin secretion follows, and is sustained until normoglycemia is restored.

First-phase insulin secretion is often represented in clinical studies by the acute insulin response to an intravenous glucose bolus. While an intravenous glucose bolus is not equivalent to an oral mixed meal, it serves as a standardized beta-cell stimulus by which first-phase insulin secretion can be carefully compared among different subjects. Further, it demonstrates the sensitivity to and insulin response of the beta cell specifically to the glucose stimulus. It is this loss of beta-cell glucose sensitivity and responsiveness that declines early in the development of type 2 diabetes, even while responses to amino acid and other stimuli are preserved.