Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus-an adaptive response to hyperglycaemia?
Upregulation of alpha cell glucagon-like peptide 1 (GLP-1) in Psammomys obesus-an adaptive response to hyperglycaemia?
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DOI：
10.1007/s00125-011-2080-1
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发表时间：
2011-06-01
期刊：
影响因子：
8.2
通讯作者：
Karlsen, A. E.
中科院分区：
文献类型：
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作者：
Hansen, A. M. K.;Boedvarsdottir, T. B.;Karlsen, A. E.
胰高血糖素样肽 1 (GLP-1) 是在进食后从肠道 L 细胞中释放出来的，在肠道 L 细胞中，它是由胰高血糖素原通过原转化酶 (PC)1/3 加工而成的。相反，在成年胰岛中，胰高血糖素原被 PC2 酶加工成胰高血糖素。该研究的目的是评估在糖尿病的发展过程中，α细胞是否产生GLP-1，进而可能触发β细胞生长。在沙鼠Psammomys obesus（P. obesus）（一种营养诱发糖尿病的啮齿动物模型）中测量了β细胞质量、GLP-1和胰岛素水平。此外，通过免疫荧光证明了α细胞中存在生物活性形式的GLP-1和PC1/3，并研究了分离的P. obesus、小鼠和人类胰岛中GLP-1的释放。在P. obesus发展为糖尿病的过程中，在门静脉中检测到GLP-1显着增加（9.8 +/- 1.5 vs 4.3 +/- 0.7 pmol/l，p < 0.05），并且胰腺提取物中（11.4 +/- 2.2 vs 5.1 +/- 1.3 pmol/g 组织，p < 0.05）。培养 24 小时后，来自高血糖动物的新鲜分离的胰岛比来自对照动物的胰岛释放更多的 GLP-1（28.2 +/- 4.4 pmol/l vs 5.8 +/- 2.4，p < 0.01）。在高葡萄糖中培养 6 天后，健康的 P. obesus 胰岛的 GLP-1 释放增加（91 +/- 9.1 pmol/l vs 28.8 +/- 6.6，p < 0.01）。还发现人类胰岛释放出高水平的 GLP-1。 PC1/3 与 α 细胞共定位较弱。在肥胖 P. obesus 中，α 细胞释放的 GLP-1 在糖尿病发展过程中上调。在暴露于高葡萄糖的胰岛中也观察到类似的反应，这支持了这样的假设：在糖尿病等代谢挑战期间，α细胞释放的 GLP-1 促进 β 细胞质量和功能的增加。
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.