Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas
Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas
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DOI：
10.1007/s00125-008-1149-y
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发表时间：
2008-12-01
期刊：
影响因子：
8.2
通讯作者：
Holst, J. J.
中科院分区：
文献类型：
--
作者：
de Heer, J.;Rasmussen, C.;Holst, J. J.
胰高血糖素样肽-1 (GLP-1) 的降血糖作用不仅基于其强大的促胰岛素作用，还基于其抑制胰高血糖素分泌的能力。令人惊讶的是，密切相关的葡萄糖依赖性促胰岛素肽（GIP）可刺激胰高血糖素释放。我们检查了强烈抑制胰高血糖素分泌的胰岛激素生长抑素是否参与了这种不同的行为。在 1.5 mmol/l 葡萄糖和因此胰岛素分泌最少的情况下，在高亲和力单克隆抗体存在的情况下研究了胰高血糖素、胰岛素和生长抑素对 20 mmol/l 葡萄糖、GLP-1、GIP 和生长抑素的反应。 生长抑素抗体和高度特异性生长抑素受体亚型 2 (SSTR2) 拮抗剂 (PRL-2903) 在分离的灌注大鼠胰腺中。在对照实验中，1 和 10 nmol/l 的 GLP-1 显着降低胰高血糖素分泌至 59.0 +/- 6.3% (p
The glucose-lowering effect of glucagon-like peptide-1 (GLP-1) is based not only upon its potent insulinotropic actions but also on its ability to restrain glucagon secretion. Surprisingly, the closely related glucose-dependent insulinotropic peptide (GIP) stimulates glucagon release. We examined whether the islet hormone somatostatin, which strongly inhibits glucagon secretion, is involved in this divergent behaviour.At 1.5 mmol/l glucose and therefore minimal insulin secretion, the glucagon, insulin and somatostatin responses to 20 mmol/l glucose, GLP-1, GIP and somatostatin were studied in the presence of a high-affinity monoclonal somatostatin antibody and of a highly specific somatostatin receptor subtype 2 (SSTR2) antagonist (PRL-2903) in the isolated perfused rat pancreas.In control experiments, GLP-1 at 1 and 10 nmol/l reduced glucagon secretion significantly to 59.0 +/- 6.3% (p