Somatostatin Is Only Partly Required for the Glucagonostatic Effect of Glucose but Is Necessary for the Glucagonostatic Effect of KATP Channel Blockers
Somatostatin Is Only Partly Required for the Glucagonostatic Effect of Glucose but Is Necessary for the Glucagonostatic Effect of KATP Channel Blockers
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DOI：
10.2337/db17-0880
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发表时间：
2018-11-01
期刊：
影响因子：
7.7
通讯作者：
Gilon, Patrick
中科院分区：
文献类型：
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作者：
Lai, Bao-Khanh;Chae, Heeyoung;Gilon, Patrick
胰高血糖素分泌的控制机制存在很大争议。特别是，生长抑素（SST）的旁分泌作用尚不清楚。我们使用灌注胰岛和原位灌注胰腺，研究了其在葡萄糖和 K-ATP 通道阻滞剂控制胰高血糖素分泌中的作用。通过比较对照组织或没有SST旁分泌影响的组织（百日咳毒素处理的胰岛，或来自Sst(-/-)小鼠的胰岛或胰腺）的胰高血糖素释放来评估SST的参与。我们发现，去除 SST 的旁分泌影响会抑制 K-ATP 通道阻滞剂或 K-ATP 通道消融抑制胰高血糖素释放的能力，这表明在对照胰岛中，K-ATP 通道阻滞剂/消融的胰高血糖素抑制作用完全由 SST 介导。相比之下，对于低葡萄糖浓度（0-7 mmol/L），对照胰岛中葡萄糖的胰高血糖素抑制作用主要与 SST 无关，但对于高浓度糖（15-30 mmol/L）则开始涉及 SST。这表明葡萄糖的胰高血糖素抑制作用仅部分取决于 SST。实时定量PCR和药理实验表明，SST的降血糖作用是由两种类型的SST受体SSTR2和SSTR3介导的。这些结果表明，SST 旁分泌影响的改变将影响胰高血糖素的释放。
The mechanisms of control of glucagon secretion are largely debated. In particular, the paracrine role of somatostatin (SST) is unclear. We studied its role in the control of glucagon secretion by glucose and K-ATP channel blockers, using perifused islets and the in situ perfused pancreas. The involvement of SST was evaluated by comparing glucagon release of control tissue or tissue without paracrine influence of SST (pertussis toxin-treated islets, or islets or pancreas from Sst(-/-) mice). We show that removal of the paracrine influence of SST suppresses the ability of K-ATP channel blockers or K-ATP channel ablation to inhibit glucagon release, suggesting that in control islets, the glucagonostatic effect of K-ATP channel blockers/ablation is fully mediated by SST. By contrast, the glucagonostatic effect of glucose in control islets is mainly independent of SST for low glucose concentrations (0-7 mmol/L) but starts to involve SST for high concentrations of the sugar (15-30 mmol/L). This demonstrates that the glucagonostatic effect of glucose only partially depends on SST. Real-time quantitative PCR and pharmacological experiments indicate that the glucagonostatic effect of SST is mediated by two types of SST receptors, SSTR2 and SSTR3. These results suggest that alterations of the paracrine influence of SST will affect glucagon release.