Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus—an adaptive response to hyperglycaemia?
| Autor: | Allan E. Karlsen, Carsten F. Gotfredsen, Jens J. Holst, J. J. Fels, R. S. Heller, Kathrin Maedler, A. M. K. Hansen, D. N. E. Nordestgaard, Thora B. Bodvarsdottir |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male endocrine system medicine.medical_specialty Endocrinology Diabetes and Metabolism Alpha (ethology) Biology Glucagon Alpha cell Islets of Langerhans Mice Downregulation and upregulation Glucagon-Like Peptide 1 Insulin-Secreting Cells Internal medicine Diabetes Mellitus Internal Medicine medicine Animals Humans Insulin Obesity Cells Cultured Cell Proliferation Dose-Response Relationship Drug digestive oral and skin physiology Middle Aged Proglucagon Adaptation Physiological Glucagon-like peptide-1 Diet Up-Regulation Disease Models Animal Glucose Endocrinology Gastrointestinal hormone Glucagon-Secreting Cells Hyperglycemia Female Beta cell Gerbillinae hormones hormone substitutes and hormone antagonists |
| Zdroj: | Diabetologia. 54:1379-1387 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-011-2080-1 |
| Popis: | 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.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.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, p0.05), and in pancreas extracts (11.4 ± 2.2 vs 5.1 ± 1.3 pmol/g tissue, p0.05). 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, p0.01). 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, p0.01). High levels of GLP-1 were also found to be released from human islets. PC1/3 colocalised weakly with alpha cells.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. |
| Databáze: | OpenAIRE |
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