Gastric Inhibitory Polypeptide and Glucagon-Like Peptide-1 in the Pathogenesis of Type 2 Diabetes

  1. Michael A. Nauck1,
  2. Birgit Baller2 and
  3. Juris J. Meier23
  1. 1From the Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Germany
  2. 2Medizinische Universitätsklinik I, St. Josef-Hospital, Ruhr-Universität Bochum, Bochum, Germany
  3. 3Larry L. Hillblom Islet Research Center, UCLA David Geffen School of Medicine, Los Angeles, California
  1. Address correspondence and reprint requests to Prof. Dr. med. Michael Nauck, Diabeteszentrum Bad Lauterberg, Kirchberg 21, D-37431 Bad Lauterberg im Harz. E-mail: m.nauck{at}


The incretin effect denominates the phenomenon that oral glucose elicits a higher insulin response than does intravenous glucose. The two hormones responsible for the incretin effect, glucose-dependent insulinotropic hormone (GIP) and glucagon-like peptide-1 (GLP-1), are secreted after oral glucose loads and augment insulin secretion in response to hyperglycemia. In patients with type 2 diabetes, the incretin effect is reduced, and there is a moderate degree of GLP-1 hyposecretion. However, the insulinotropic response to GLP-1 is well maintained in type 2 diabetes. GIP is secreted normally or hypersecreted in type 2 diabetes; however, the responsiveness of the endocrine pancreas to GIP is greatly reduced. In ∼50% of first-degree relatives of patients with type 2 diabetes, similarly reduced insulinotropic responses toward exogenous GIP can be observed, without significantly changed secretion of GIP or GLP-1 after oral glucose. This opens the possibility that a reduced responsiveness to GIP is an early step in the pathogenesis of type 2 diabetes. On the other hand, this provides a basis to use incretin hormones, especially GLP-1 and its derivatives, to replace a deficiency in incretin-mediated insulin secretion in the treatment of type 2 diabetes.


  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.

    • Accepted May 18, 2004.
    • Received March 9, 2004.
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