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01.06.2011 | Article

Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus—an adaptive response to hyperglycaemia?

verfasst von: A. M. K. Hansen, T. B. Bödvarsdottir, D. N. E. Nordestgaard, R. S. Heller, C. F. Gotfredsen, K. Maedler, J. J. Fels, J. J. Holst, A. E. Karlsen

Erschienen in: Diabetologia | Ausgabe 6/2011

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Abstract

Aims/hypothesis

The hormone glucagon-like peptide 1 (GLP-1) is released in response to a meal from the intestinal L-cells, where it is processed from proglucagon by the proconvertase (PC)1/3. In contrast, in the adult islets proglucagon is processed to glucagon by the PC2 enzyme. The aim of the study was to evaluate if, during the development of diabetes, alpha cells produce GLP-1 that, in turn, might trigger beta cell growth.

Methods

Beta cell mass, GLP-1 and insulin levels were measured in the gerbil Psammomys obesus (P. obesus), a rodent model of nutritionally induced diabetes. Furthermore, the presence of biologically active forms of GLP-1 and PC1/3 in alpha cells was demonstrated by immunofluorescence, and the release of GLP-1 from isolated P. obesus, mouse and human islets was investigated.

Results

During the development of diabetes in P. obesus, a significant increase in GLP-1 was detected in the portal vein (9.8 ± 1.5 vs 4.3 ± 0.7 pmol/l, p < 0.05), and in pancreas extracts (11.4 ± 2.2 vs 5.1 ± 1.3 pmol/g tissue, p < 0.05). Freshly isolated islets from hyperglycaemic animals released more GLP-1 following 24 h culture than islets from control animals (28.2 ± 4.4 pmol/l vs 5.8 ± 2.4, p < 0.01). GLP-1 release was increased from healthy P. obesus islets following culture in high glucose for 6 days (91 ± 9.1 pmol/l vs 28.8 ± 6.6, p < 0.01). High levels of GLP-1 were also found to be released from human islets. PC1/3 colocalised weakly with alpha cells.

Conclusions/interpretation

GLP-1 release from alpha cells is upregulated in P. obesus during the development of diabetes. A similar response is seen in islets exposed to high glucose, which supports the hypothesis that GLP-1 released from alpha cells promotes an increase in beta cell mass and function during metabolic challenge such as diabetes.

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Titel: Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus—an adaptive response to hyperglycaemia?
verfasst von: A. M. K. Hansen
T. B. Bödvarsdottir
D. N. E. Nordestgaard
R. S. Heller
C. F. Gotfredsen
K. Maedler
J. J. Fels
J. J. Holst
A. E. Karlsen
Publikationsdatum: 01.06.2011
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 6/2011
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2080-1

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Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus—an adaptive response to hyperglycaemia?

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