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首页> 外文期刊>Cellular Physiology and Biochemistry >Dynamic Profiling of Insulin Secretion and ATP Generation in Isolated Human and Mouse Islets Reveals Differential Glucose Sensitivity
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Dynamic Profiling of Insulin Secretion and ATP Generation in Isolated Human and Mouse Islets Reveals Differential Glucose Sensitivity

机译：分离的人胰岛和小鼠胰岛中胰岛素分泌和ATP生成的动态分析揭示了差异性葡萄糖敏感性。

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>Background/Aims: Rodent islets are often used for basic science research but they do not always recapitulate signalling events in human islets. This study evaluated the glucose-dependent responses of human and mouse islets in terms of dynamic insulin secretion, metabolic coupling and the role of glucose transporters. Methods: Glucose-induced insulin secretion from isolated mouse and human islets was profiled by perifusion and islet ATP levels were measured by chemoluminescence assay. Glucose transporter expression was determined by qPCR and western blotting. Results: Human islets show a left-shifted glucose concentration-insulin secretion profile compared to mouse islets. These data are consistent with glucose transporter expression, with human islets expressing mainly GLUT1 and GLUT3, and GLUT2 being the predominant transporter in mouse islets. Using the GLUT1 inhibitor STF-31 we unveiled an important role for GLUT1 for differences in glucose-induced insulin secretion profiles observed between the two species. Conclusion: The high affinity of GLUT1/3 for glucose reflects the left-shifted glucose-induced insulin secretory response of human islets and the impairment of insulin secretion from human islets after STF-31 treatment indicates an important role for GLUT1 in human islet stimulus-secretion coupling. Our data provide further insight into key differences between insulin secretion regulation in mouse and human islets.
机译：> 背景/目标： 啮齿动物小岛通常用于基础科学研究，但它们并不总是概括人类小岛中的信号事件。这项研究根据动态胰岛素分泌，代谢偶联和葡萄糖转运蛋白的作用评估了人类和小鼠胰岛的葡萄糖依赖性反应。 方法： 通过灌流分析葡萄糖诱导的离体小鼠和人胰岛胰岛素分泌，并通过化学发光法测定胰岛ATP水平。通过qPCR和蛋白质印迹确定葡萄糖转运蛋白表达。 结果： 与小鼠胰岛相比，人类胰岛的葡萄糖浓度-胰岛素分泌曲线向左移动。这些数据与葡萄糖转运蛋白表达一致，其中人类胰岛主要表达GLUT1和GLUT3，而GLUT2是小鼠胰岛中的主要转运蛋白。使用GLUT1抑制剂STF-31，我们揭示了GLUT1的重要作用，因为这两个物种之间观察到的葡萄糖诱导的胰岛素分泌曲线存在差异。 结论： GLUT1 / 3对葡萄糖的高亲和力反映了STF后左移葡萄糖诱导的人胰岛胰岛素分泌反应以及人胰岛胰岛素分泌受损-31治疗表明GLUT1在人胰岛刺激-分泌偶联中具有重要作用。我们的数据提供了对小鼠和人类胰岛中胰岛素分泌调节之间关键差异的进一步了解。

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