Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Viewpoint
  • Published:

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

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Nauck MA et al. (2004) Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes. Diabetes 53 (Suppl 3): S190–S196

    Article  CAS  Google Scholar 

  2. Drucker DJ and Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368: 1696–1705

    Article  CAS  Google Scholar 

  3. Toft-Nielsen MB et al. (2001) Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 86: 3717–3723

    Article  CAS  Google Scholar 

  4. Muscelli E et al. (2008) Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients. Diabetes 57: 1340–1348

    Article  CAS  Google Scholar 

  5. Theodorakis MJ et al. (2006) Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am J Physiol Endocrinol Metab 290: E550–E559

    Article  CAS  Google Scholar 

  6. Vollmer K et al. (2008) Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 57: 678–687

    Article  CAS  Google Scholar 

  7. Laakso M et al. (2008) Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study. Diabetologia 51: 502–511

    Article  CAS  Google Scholar 

  8. Vilsbøll T et al. (2003) Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab 88: 2706–2713

    Article  Google Scholar 

  9. Meier JJ et al. (2005) Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes. Diabetologia 48: 1872–1881

    Article  CAS  Google Scholar 

  10. Schou JH et al. (2005) Normal secretion and action of the gut incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in young men with low birth weight. J Clin Endocrinol Metab 90: 4912–4919

    Article  CAS  Google Scholar 

Download references

Author information

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

Authors
  1. Juris J Meier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael A Nauck
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael A Nauck.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpendmet0946

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing