Basal receptor activation by locally produced glucagon-like peptide-1 contributes to maintaining beta-cell function

Mol Endocrinol. 2005 May;19(5):1373-82. doi: 10.1210/me.2004-0350. Epub 2005 Jan 27.


Glucagon-like peptide 1 (GLP-1) is a physiological stimulus of pancreatic beta-cell function. This enteroendocrine hormone is produced by intestinal L cells, and is delivered via the bloodstream to GLP-1 receptors (GLP-1Rs) on pancreatic beta-cells. In addition, there is evidence that beta-cell GLP-1Rs maintain sustained basal activity even in the absence of intestinal peptide, an observation that has raised the question whether these receptors have some degree of ligand-independent function. Here, we provide an alternative explanation for basal receptor activity based on our finding that biologically relevant amounts of fully processed GLP-1 are locally generated by insulinoma cell lines, as well as by alpha-cells of isolated rat islets in primary culture. Presence of GLP-1 was established by immunocytochemistry, as well as by selective ELISAs and bioassays of cell supernatants. A GLP-1R antagonist significantly reduced insulin secretion/production in beta-TC-6 insulinoma cells and isolated rat islets, suggesting a functionally important loop between locally produced GLP-1 and its cognate receptor. Treatment with this antagonist also inhibited the growth of beta-TC-6 cells. These observations provide novel insight into the function of insulin-producing cell lines and native beta-cells during in vitro culture, and they support the idea that locally produced GLP-1 may play a role in intra-islet regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Enzyme-Linked Immunosorbent Assay
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Islets of Langerhans / metabolism*
  • Male
  • Peptide Fragments / metabolism*
  • Protein Precursors / metabolism*
  • Radioimmunoassay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / metabolism*


  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Protein Precursors
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon