A Local Glucagon-Like Peptide 1 (GLP-1) System in Human Pancreatic Islets

Diabetologia. 2012 Dec;55(12):3262-72. doi: 10.1007/s00125-012-2716-9. Epub 2012 Sep 11.

Abstract

Aims/hypothesis: Glucagon-like peptide 1 (GLP-1) is a major incretin, mainly produced by the intestinal L cells, with beneficial actions on pancreatic beta cells. However, while in vivo only very small amounts of GLP-1 reach the pancreas in bioactive form, some observations indicate that GLP-1 may also be produced in the islets. We performed comprehensive morphological, functional and molecular studies to evaluate the presence and various features of a local GLP-1 system in human pancreatic islet cells, including those from type 2 diabetic patients.

Methods: The presence of insulin, glucagon, GLP-1, proconvertase (PC) 1/3 and PC2 was determined in human pancreas by immunohistochemistry with confocal microscopy. Islets were isolated from non-diabetic and type 2 diabetic donors. GLP-1 protein abundance was evaluated by immunoblotting and matrix-assisted laser desorption-ionisation-time of flight (MALDI-TOF) mass spectrometry. Single alpha and beta cell suspensions were obtained by enzymatic dissociation and FACS sorting. Glucagon and GLP-1 release were measured in response to nutrients.

Results: Confocal microscopy showed the presence of GLP-1-like and PC1/3 immunoreactivity in subsets of alpha cells, whereas GLP-1 was not observed in beta cells. The presence of GLP-1 in isolated islets was confirmed by immunoblotting, followed by mass spectrometry. Isolated islets and alpha (but not beta) cell fractions released GLP-1, which was regulated by glucose and arginine. PC1/3 (also known as PCSK1) gene expression was shown in alpha cells. GLP-1 release was significantly higher from type 2 diabetic than from non-diabetic isolated islets.

Conclusions/interpretation: We have shown the presence of a functionally competent GLP-1 system in human pancreatic islets, which resides in alpha cells and might be modulated by type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Secreting Cells / metabolism*
  • Humans
  • Immunohistochemistry
  • Insulin / metabolism*
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Pancreas / metabolism

Substances

  • Insulin
  • Glucagon-Like Peptide 1
  • Glucagon