Oxford Center for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, United Kingdom.
Annu Rev Physiol. 2013;75:155-79. doi: 10.1146/annurev-physiol-030212-183754. Epub 2012 Sep 4.
Pancreatic β cells secrete insulin, the body's only hormone capable of lowering plasma glucose levels. Impaired or insufficient insulin secretion results in diabetes mellitus. The β cell is electrically excitable; in response to an elevation of glucose, it depolarizes and starts generating action potentials. The electrophysiology of mouse β cells and the cell's role in insulin secretion have been extensively investigated. More recently, similar studies have been performed on human β cells. These studies have revealed numerous and important differences between human and rodent β cells. Here we discuss the properties of human pancreatic β cells: their glucose sensing, the ion channel complement underlying glucose-induced electrical activity that culminates in exocytotic release of insulin, the cellular control of exocytosis, and the modulation of insulin secretion by circulating hormones and locally released neurotransmitters. Finally, we consider the pathophysiology of insulin secretion and the interactions between genetics and environmental factors that may explain the current diabetes epidemic.
胰岛β细胞分泌胰岛素,这是人体唯一能够降低血糖水平的激素。胰岛素分泌受损或不足会导致糖尿病。β细胞具有电兴奋性;当血糖升高时,它会去极化并开始产生动作电位。小鼠β细胞的电生理学及其在胰岛素分泌中的作用已经得到了广泛的研究。最近,对人类β细胞也进行了类似的研究。这些研究揭示了人类和啮齿动物β细胞之间存在许多重要的差异。在这里,我们讨论人胰岛β细胞的特性:它们的葡萄糖感应、离子通道组成,这些通道在葡萄糖诱导的电活动中起作用,最终导致胰岛素的胞吐释放、胞吐的细胞控制以及循环激素和局部释放的神经递质对胰岛素分泌的调节。最后,我们考虑胰岛素分泌的病理生理学以及遗传和环境因素之间的相互作用,这些因素可能解释了当前的糖尿病流行。