Distribution of glucagon receptors on hormone-specific endocrine cells of rat pancreatic islets

Endocrinology. 1996 Nov;137(11):5119-25. doi: 10.1210/endo.137.11.8895386.


Glucagon is insulinotropic, but it remains uncertain whether the insulinotropic action is mediated directly by glucagon receptors expressed on beta-cells or by cross-binding to the insulinotropic glucagon-like peptide-1 (GLP-1) receptor known to be expressed on beta-cells. Binding of [125I]glucagon to GLP-1 receptors and not to glucagon receptors has been reported in tumor-derived beta-cells (15). The objectives of the current study were to use receptor-binding techniques and a glucagon receptor-specific antiserum to determine whether glucagon receptors are present on beta-cells. Specific binding (7.2 +/- 0.8%) of [125I]GLP-1 to beta TC-3 cells was displaced equivalently with GLP-1 and exendin-(9-39) )Kd = 0.9 and 0.4 nM. respectively), whereas approximately 700-fold higher concentrations of glucagon were required for equal displacement (Kd = 400 nM). Binding of [125I]glucagon to beta TC-3 cells (approximately 1%) was displaced equivalently with 1 microM glucagon, GLP-1, or exendin-(9-39). These observations support earlier findings that beta TC-3 cells do not express functional glucagon receptors. However, specific binding of [125I]glucagon was observed on INS-1 cells (2.3 +/- 0.2%); this was displaced with glucagon (Kd = 1 nM), but not 1 microM GLP-1 or exendin-(9-39). To examine the distribution of glucagon receptors on native beta-cells, dispersed cultured rat islets were immunostained for glucagon, somatostatin, or insulin in combination with a polyclonal rabbit antiserum raised to an extracellular portion of the glucagon receptor (KD-14). The glucagon receptor antiserum colocalized staining with approximately 97% of immunoreactive insulin cells, 9% of immunoreactive glucagon cells, and 11% of immunoreactive somatostatin cells. Perfusion of the rat pancreas with concentrations of glucagon as low as 10(-12) M resulted in significant insulin release. These results suggest that whereas the tumor-derived beta-cell line beta TC-3 does not express functional glucagon receptors, INS-1 cells and isolated rat pancreatic beta-cells have specific glucagon receptors, as do a subpopulation of alpha- and delta-cells. A model is proposed for the role of glucagon in islet hormone secretion during feeding and fasting.

Publication types

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

MeSH terms

  • Animals
  • Binding, Competitive
  • Cell Line
  • Cells, Cultured
  • Eating
  • Fasting
  • Female
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Immunohistochemistry
  • Insulin / metabolism
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism*
  • Kinetics
  • Male
  • Models, Biological
  • Peptide Fragments / metabolism*
  • Protein Precursors / metabolism*
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / analysis
  • Receptors, Glucagon / metabolism*
  • Somatostatin / metabolism


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