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Original Research
Incretin action in the pancreas: Potential promise, possible perils, and pathological pitfalls
Daniel J. Drucker
Diabetes 2013 Jul; DB_130822. https://doi.org/10.2337/db13-0822
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Abstract

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones that control secretion of insulin, glucagon and somatostatin to facilitate glucose disposal. The actions of incretin hormones are terminated via enzymatic cleavage by dipeptidyl peptidase-4 (DPP-4), and through renal clearance. GLP-1 and GIP promote β-cell proliferation and β-cell survival in rodent β-cells. DPP-4 inhibitors expand β-cell and reduce α-cell mass and inhibit glucagon secretion in preclinical studies however whether incretin-based therapies sustain functional β-cell mass in human diabetic subjects remains unclear. GLP-1 and GIP exert their actions predominantly through unique G protein coupled receptors expressed on β-cells and other pancreatic cell types. Accurate localization of incretin receptor expression in pancreatic ductal or acinar cells in normal or diabetic human pancreas is challenging as antisera employed for detection of the GLP-1R are often neither sufficiently sensitive nor specific to yield reliable data. We review recent advances and controversies in incretin hormone action in the pancreas and contrast established mechanisms with areas of uncertainty. Furthermore, we highlight methodological challenges and pitfalls and outline key areas requiring additional scientific investigation.

  • Received May 23, 2013.
  • Accepted June 19, 2013.
  • © 2013 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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Incretin action in the pancreas: Potential promise, possible perils, and pathological pitfalls
Daniel J. Drucker
Diabetes Jul 2013, DB_130822; DOI: 10.2337/db13-0822

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Incretin action in the pancreas: Potential promise, possible perils, and pathological pitfalls
Daniel J. Drucker
Diabetes Jul 2013, DB_130822; DOI: 10.2337/db13-0822
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© 2019 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X.