The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice.

Journal Article (Journal Article)

Glucagon-like peptide 1 (GLP-1) is necessary for normal gluco-regulation, and it has been widely presumed that this function reflects the actions of GLP-1 released from enteroendocrine L cells. To test the relative importance of intestinal versus pancreatic sources of GLP-1 for physiological regulation of glucose, we administered a GLP-1R antagonist, exendin-[9-39] (Ex9), to mice with tissue-specific reactivation of the preproglucagon gene (Gcg). Ex9 impaired glucose tolerance in wild-type mice but had no impact on Gcg-null or GLP-1R KO mice, suggesting that Ex9 is a true and specific GLP-1R antagonist. Unexpectedly, Ex-9 had no effect on blood glucose in mice with restoration of intestinal Gcg. In contrast, pancreatic reactivation of Gcg fully restored the effect of Ex9 to impair both oral and i.p. glucose tolerance. These findings suggest an alternative model whereby islet GLP-1 also plays an important role in regulating glucose homeostasis.

Full Text

Duke Authors

Cited Authors

  • Chambers, AP; Sorrell, JE; Haller, A; Roelofs, K; Hutch, CR; Kim, K-S; Gutierrez-Aguilar, R; Li, B; Drucker, DJ; D'Alessio, DA; Seeley, RJ; Sandoval, DA

Published Date

  • April 4, 2017

Published In

Volume / Issue

  • 25 / 4

Start / End Page

  • 927 - 934.e3

PubMed ID

  • 28325479

Pubmed Central ID

  • PMC5385998

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2017.02.008


  • eng

Conference Location

  • United States