The incretin effect: Regulation of insulin secretion and glucose tolerance by GI hormones

David A. D’alessio, Benedikt A. Aulinger, Marzieh Salehi

Research output: Chapter in Book/Report/Conference proceedingChapter


The concentration of glucose in the blood is a highly regulated physiologic parameter. The adaptive significance of maintaining glucose levels within narrow bounds is probably related to minimization of fluid shifts, appropriate allocation of glucose to storage depots, and retention of calories. The system for glucose regulation is complex and very effective. For example, nondiabetic humans have the capacity to eat large carbohydrate meals, with only minor, 30% to 50%, changes in circulating glucose concentrations that are typically returned to basal levels within 1 to 2 hours. Signaling by the islet hormone insulin is the principle means of shifting glucose from the circulation into cells and the control of insulin secretion is at the core of normal glucose tolerance. The islet -cell is regulated by the interaction of substrate, neural, and hormonal stimuli. An increase in ambient glucose is the best established stimulus for insulin release, and is essential for normal secretion in vivo since the response to other physiologic -cell stimuli are substantially reduced at basal glucose levels. However, it is clear from the pattern of -cell secretory rates after meals that other factors also have important roles in this process. Insulin secretion is most pronounced in the early part of meals, before a peak in blood glucose (1) suggesting that other factors, in addition to hyperglycemia, stimulate the -cell after meals. For effective homeostasis it is important that insulin secretion should not change as a strictly linear function of plasma glycemia but rather preempt major changes in blood glucose. In other words, the -cells should anticipate an increase in glycemia rather than simply chasing the rising glucose levels. This system has at its core inputs from the gastrointestinal (GI) tract that act as a feed forward mechanism to link nutrient absorption with insulin secretion in order to promote efficient nutrient assimilation (2-4). In addition, there are neural stimuli to the -cell that play a role in physiologic insulin secretion (5). Signals carried by parasympathetic nerves contribute to anticipatory insulin secretion, termed cephalic insulin release, and also to the postprandial insulin response. Thus, the model that has emerged from a large body of research over the last three decades is that the insulin response to eating is controlled by a system that integrates circulating glucose levels, neural inputs, and stimulation by hormones released from the GI tract to allow glycemia to be restored rapidly, and without hypoglycemia.

Original languageEnglish (US)
Title of host publicationDiabetes
Subtitle of host publicationTranslating Research into Practice
PublisherCRC Press
Number of pages16
ISBN (Electronic)9781420047363
ISBN (Print)1420043714, 9781420043716
StatePublished - Jan 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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