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Is secretion of glucagon-like peptide-1 reduced in type 2 diabetes mellitus?

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 606–607 (2008)Cite this article

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Postprandial augmentation of insulin secretion by gastrointestinal peptide hormones—the so-called 'incretin effect'—is reduced in patients with type 2 diabetes mellitus, an observation that has led to investigation of potential mechanisms for this defect.1,2 The incretin effect is mediated by the secretion and insulinotropic action of gastric inhibitory polypeptide and glucagon-like peptide-1 (GLP-1).1 Secretion of gastric inhibitory polypeptide is normal or slightly elevated in patients with type 2 diabetes mellitus,1 whereas the insulinotropic action of this hormone is almost completely lost.1,2 The situation is somewhat different for GLP-1, as the insulinotropic action of this hormone is relatively well-preserved.1,2 By contrast, postprandial GLP-1 secretion has been found to be reduced in some studies.3 In light of this finding, treatment with GLP-1 receptor agonists, such as exenatide, has been suggested to serve as a true replacement therapy that substitutes for a pathophysiological defect in type 2 diabetes mellitus.

Upon closer inspection, however, the situation is more complex. Although the insulinotropic efficacy of GLP-1 in patients with type 2 diabetes mellitus is certainly better preserved than that of gastric inhibitory polypeptide, it still remains impaired when compared with healthy individuals.1 Some studies have reported reduced GLP-1 secretion in patients with type 2 diabetes mellitus,3,4 whereas other studies (including our own) have failed to detect lower GLP-1 levels in this patient group.5,6 A number of questions, therefore, need to be addressed. Is secretion of GLP-1 truly impaired in patients with type 2 diabetes mellitus? If so, is impaired GLP-1 secretion a primary defect that predisposes individuals towards development of this disease or does it occur as a consequence of the diabetic state or its complications? Finally, does reduced secretion of GLP-1 contribute to the impaired postprandial insulin secretion typical of this patient group? In this Viewpoint, we discuss the evidence for and against reduced GLP-1 secretion in the etiology of type 2 diabetes mellitus.

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References

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Authors and Affiliations

  1. JJ Meier is an Assistant Professor of Experimental Gastroenterology and Metabolism at the Department of Medicine I, St Josef-Hospital, Ruhr-University Bochum, and MA Nauck is Head Physician at the Diabeteszentrum Bad Lauterberg im Harz, Germany.,

    Juris J Meier & Michael A Nauck

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  1. Juris J Meier
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  2. Michael A Nauck
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Correspondence to Michael A Nauck.

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Meier, J., Nauck, M. Is secretion of glucagon-like peptide-1 reduced in type 2 diabetes mellitus?. Nat Rev Endocrinol 4, 606–607 (2008). https://doi.org/10.1038/ncpendmet0946

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