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The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice.

Publication ,  Journal Article
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 ...
Published in: Cell Metab
April 4, 2017

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.

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Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

April 4, 2017

Volume

25

Issue

4

Start / End Page

927 / 934.e3

Location

United States

Related Subject Headings

  • Reproducibility of Results
  • Proglucagon
  • Phenotype
  • Pancreas
  • Organ Specificity
  • Mice, Inbred C57BL
  • Male
  • Injections, Intraperitoneal
  • Homeostasis
  • Glucose Tolerance Test
 

Citation

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Chicago
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Chambers, A. P., Sorrell, J. E., Haller, A., Roelofs, K., Hutch, C. R., Kim, K.-S., … Sandoval, D. A. (2017). The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice. Cell Metab, 25(4), 927-934.e3. https://doi.org/10.1016/j.cmet.2017.02.008
Chambers, Adam P., Joyce E. Sorrell, April Haller, Karen Roelofs, Chelsea R. Hutch, Ki-Suk Kim, Ruth Gutierrez-Aguilar, et al. “The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice.Cell Metab 25, no. 4 (April 4, 2017): 927-934.e3. https://doi.org/10.1016/j.cmet.2017.02.008.
Chambers AP, Sorrell JE, Haller A, Roelofs K, Hutch CR, Kim K-S, et al. The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice. Cell Metab. 2017 Apr 4;25(4):927-934.e3.
Chambers, Adam P., et al. “The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice.Cell Metab, vol. 25, no. 4, Apr. 2017, pp. 927-934.e3. Pubmed, doi:10.1016/j.cmet.2017.02.008.
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. The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice. Cell Metab. 2017 Apr 4;25(4):927-934.e3.
Journal cover image

Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

April 4, 2017

Volume

25

Issue

4

Start / End Page

927 / 934.e3

Location

United States

Related Subject Headings

  • Reproducibility of Results
  • Proglucagon
  • Phenotype
  • Pancreas
  • Organ Specificity
  • Mice, Inbred C57BL
  • Male
  • Injections, Intraperitoneal
  • Homeostasis
  • Glucose Tolerance Test