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Diabetologia
Published in: Diabetologia 12/2012

01-12-2012 | Article

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

Authors: P. Marchetti, R. Lupi, M. Bugliani, C. L. Kirkpatrick, G. Sebastiani, F. A. Grieco, S. Del Guerra, V. D’Aleo, S. Piro, L. Marselli, U. Boggi, F. Filipponi, L. Tinti, L. Salvini, C. B. Wollheim, F. Purrello, F. Dotta

Published in: Diabetologia | Issue 12/2012

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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.
Appendix
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Metadata
Title
A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets
Authors
P. Marchetti
R. Lupi
M. Bugliani
C. L. Kirkpatrick
G. Sebastiani
F. A. Grieco
S. Del Guerra
V. D’Aleo
S. Piro
L. Marselli
U. Boggi
F. Filipponi
L. Tinti
L. Salvini
C. B. Wollheim
F. Purrello
F. Dotta
Publication date
01-12-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 12/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2716-9

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