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

Research output: Contribution to journalJournal articleResearchpeer-review

A M K Hansen, T B Bödvarsdottir, D N E Nordestgaard, R S Heller, C F Gotfredsen, K Maedler, JJ Fels, Jens Juul Holst, AE Karlsen

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.
Original languageEnglish
JournalDiabetologia
Volume54
Issue number6
Pages (from-to)1379-87
Number of pages9
ISSN0012-186X
DOIs
Publication statusPublished - 2011

    Research areas

  • Adaptation, Physiological, Adult, Animals, Cell Proliferation, Cells, Cultured, Diabetes Mellitus, Diet, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Gerbillinae, Glucagon-Like Peptide 1, Glucagon-Secreting Cells, Glucose, Humans, Hyperglycemia, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Male, Mice, Middle Aged, Obesity, Up-Regulation

ID: 38474871