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

普吕卡贡 内科学 内分泌学 α细胞 胰高血糖素样肽-1 胰高血糖素 小岛 下调和上调 β细胞 胰岛素 生物 肠内分泌细胞 糖尿病 胰腺激素 化学 2型糖尿病 激素 医学 胰岛素抵抗 内分泌系统 生物化学 基因
作者
Ann Maria Kruse Hansen,Thóra B. Bödvarsdottir,D. N. E. Nordestgaard,R. Scott Heller,Carsten F. Gotfredsen,Kathrin Maedler,Johannes Fels,Jens J. Holst,Allan E. Karlsen
出处
期刊:Diabetologia [Springer Science+Business Media]
卷期号:54 (6): 1379-1387 被引量:75
标识
DOI:10.1007/s00125-011-2080-1
摘要

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, 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.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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