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Horm Metab Res 2004; 36(11/12): 859-866
DOI: 10.1055/s-2004-826176
Review
© Georg Thieme Verlag KG Stuttgart · New York

GIP as a Potential Therapeutic Agent?

J.  J.  Meier1 , M.  A.  Nauck2
  • 1Larry Hillblom Islet Research Center, UCLA School of Medicine, Los Angeles, USA
  • 2Diabeteszentrum Bad Lauterberg, Germany
Further Information

Publication History

Received 17 August 2004

Accepted after revision 22 August 2004

Publication Date:
18 January 2005 (online)

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Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is released from K-cells in the gut after meal ingestion, and acts in concert with glucagon-like peptide 1 (GLP-1) to augment glucose-stimulated insulin secretion. While derivatives of GLP-1 are under active investigation for the treatment of type 2 diabetes, the case is different for GIP. Indeed, the insulinotropic effect of GIP is almost absent in patients with type 2 diabetes. In addition, the unfavourable pharmacokinetic profile of native GIP obviates its clinical application. Different analogues of GIP exhibiting prolonged stability and enhanced biological potency have been generated in order improve the anti-diabetic properties of GIP. However, glucose-normalisation, as is typically observed during the intravenous administration of GLP-1 in patients with type 2 diabetes, has not yet been achieved with GIP or its derivatives. Since GIP appears to play a role in lipid physiology and elevated levels of GIP have been associated with obesity, antagonising GIP action has been proposed as a therapeutic strategy for obesity. This concept has recently been reinforced by the observation that GIP receptor knock-out mice are protected from high-fat diet-induced obesity. However, eliminating the effect of endogenous GIP may at the same time impair postprandial insulin secretion, thereby severely disturbing glucose homeostasis. Therefore, therapeutic strategies based on either augmenting or antagonising GIP action are far from being established alternatives for the future therapy of type 2 diabetes or obesity.

Key words

GIP - Gastric inhibitory polypeptide - Type 2 diabetes - Obesity - Insulin secretion

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Dr. J. J. Meier

Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine

24-130 Warren Hall · 900 Veteran Avenue · Los Angeles · CA 90095 · USA

Phone: +1 (310) 206 72 36

Fax: +1 (310) 206 53 68

Email: jmeier@mednet.ucla.edu

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