Incretins and Regulation of Insulin Secretion

  • Michael A. Nauck
  • Juris J. Meier


The incretin effect is the phenomenon whereby oral glucose elicits a greater insulin secretory response than an intravenous administration of glucose, even if the same glycemic profile is obtained (“isoglycemia”) or even exceeded. The incretin effect mainly is the results of the secretion, from gut endocrine cells, of incretin hormones, which is stimulated by the ingestion and absorption of nutrients. The main incretin hormone is gastric inhibitory polypeptide (glucose-dependent insulinotropic polypeptide, GIP), produced in and secreted from upper intestinal K cells. A second incretin hormone, glucagon-like peptide-1 (GLP-1), is synthesized mainly in lower intestinal L cells. Both incretin hormones stimulate insulin secretion by interacting with specific receptors on endocrine pancreatic beta cells. This augmentation is prominent at high glucose concentrations, but stops at glucose concentrations slightly below fasting values. In patients with type 2 diabetes, the incretin effect is reduced and the reason is that GIP has lost most of its insulinotropic activity. GLP-1, on the other hand, has preserved activity, even in patients with type 2 diabetes. In addition to its insulinotropic activity, it also suppresses glucagon, retards gastric emptying, reduces appetite and food intake, and can inhibit beta-cell apoptosis and promote beta-cell regeneration and neogenesis. Therefore, these properties of GLP-1 can be exploited to treat type 2 diabetes, both in the form of incretin mimetics (GLP-1 receptor agonists) and DPP-4 inhibitors (preventing degradation and inactivation of incretin hormones by the proteolytic enzyme dipeptidyl peptidase-4).


Insulin Secretion Gastric Emptying Gastric Inhibitory Polypeptide Incretin Hormone Incretin Effect 
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Copyright information

© Springer 2008

Authors and Affiliations

  • Michael A. Nauck
    • 1
  • Juris J. Meier
    • 2
  1. 1.Diabeteszentrum Bad LauterbergBad LauterbergGermany
  2. 2.Medizinische Klinik I, St. Josef-HospitalKlinikum der Ruhr-Universität BochumBochumGermany

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