title: A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Endocrinology and Metabolism, University of Pisa, Via Paradisa 2, Pisa, Italy. piero.marchetti@med.unipi.it
authors.forename: P
authors.initials: P
authors.lastname: Marchetti
authors.forename: R
authors.initials: R
authors.lastname: Lupi
authors.forename: M
authors.initials: M
authors.lastname: Bugliani
authors.forename: C L
authors.initials: CL
authors.lastname: Kirkpatrick
authors.forename: G
authors.initials: G
authors.lastname: Sebastiani
authors.forename: F A
authors.initials: FA
authors.lastname: Grieco
authors.forename: S
authors.initials: S
authors.lastname: Del Guerra
authors.forename: V
authors.initials: V
authors.lastname: D'Aleo
authors.forename: S
authors.initials: S
authors.lastname: Piro
authors.forename: L
authors.initials: L
authors.lastname: Marselli
authors.forename: U
authors.initials: U
authors.lastname: Boggi
authors.forename: F
authors.initials: F
authors.lastname: Filipponi
authors.forename: L
authors.initials: L
authors.lastname: Tinti
authors.forename: L
authors.initials: L
authors.lastname: Salvini
authors.forename: C B
authors.initials: CB
authors.lastname: Wollheim
authors.forename: F
authors.initials: F
authors.lastname: Purrello
authors.forename: F
authors.initials: F
authors.lastname: Dotta
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism
chemical_list: D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon