Article

Diabetologia

, Volume 55, Issue 12, pp 3262-3272

A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets

  • P. MarchettiAffiliated withDepartment of Endocrinology and Metabolism, University of PisaUnit of Endocrinology and Metabolism of Transplantation, Azienda Ospedaliera Universitaria Pisana (AOUP) Email author 
  • , R. LupiAffiliated withDepartment of Medicine, Azienda Ospedaliera Universitaria Pisana (AOUP)
  • , M. BuglianiAffiliated withDepartment of Endocrinology and Metabolism, University of Pisa
  • , C. L. KirkpatrickAffiliated withDepartment of Cell Physiology and Metabolism, University of Geneva
  • , G. SebastianiAffiliated withDiabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, University of SienaFondazione Umberto Di Mario
  • , F. A. GriecoAffiliated withDiabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, University of SienaFondazione Umberto Di Mario
  • , S. Del GuerraAffiliated withDepartment of Endocrinology and Metabolism, University of Pisa
  • , V. D’AleoAffiliated withDepartment of Endocrinology and Metabolism, University of Pisa
  • , S. PiroAffiliated withDepartment of Internal Medicine, University of Catania
    • , L. MarselliAffiliated withDepartment of Endocrinology and Metabolism, University of Pisa
    • , U. BoggiAffiliated withUnit of General Surgery and Transplantation in Uraemic and Diabetic Patients, Azienda Ospedaliera Universitaria Pisana (AOUP)
    • , F. FilipponiAffiliated withUnit of General Surgery and Liver Transplantation, Azienda Ospedaliera Universitaria Pisana (AOUP)
    • , L. TintiAffiliated withDepartment of Endocrinology and Metabolism, University of PisaToscana Life Sciences Foundation
    • , L. SalviniAffiliated withDepartment of Endocrinology and Metabolism, University of PisaToscana Life Sciences Foundation
    • , C. B. WollheimAffiliated withDepartment of Cell Physiology and Metabolism, University of Geneva
    • , F. PurrelloAffiliated withDepartment of Internal Medicine, University of Catania
    • , F. DottaAffiliated withDiabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, University of SienaFondazione Umberto Di Mario

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.

Keywords

Alpha cells GLP-1 Glucagon Pancreatic islets