The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska Sjukhuset L1:03, 17176, Stockholm, Sweden.
Sci Rep. 2020 Nov 19;10(1):20145. doi: 10.1038/s41598-020-76863-z.
The secretion of glucagon by pancreatic alpha cells is regulated by a number of external and intrinsic factors. While the electrophysiological processes linking a lowering of glucose concentrations to an increased glucagon release are well characterized, the evidence for the identity and function of the glucose sensor is still incomplete. In the present study we aimed to address two unsolved problems: (1) do individual alpha cells have the intrinsic capability to regulate glucagon secretion by glucose, and (2) is glucokinase the alpha cell glucose sensor in this scenario. Single cell RT-PCR was used to confirm that glucokinase is the main glucose-phosphorylating enzyme expressed in rat pancreatic alpha cells. Modulation of glucokinase activity by pharmacological activators and inhibitors led to a lowering or an increase of the glucose threshold of glucagon release from single alpha cells, measured by TIRF microscopy, respectively. Knockdown of glucokinase expression resulted in a loss of glucose control of glucagon secretion. Taken together this study provides evidence for a crucial role of glucokinase in intrinsic glucose regulation of glucagon release in rat alpha cells.
胰岛α细胞分泌胰高血糖素受多种内外因素调节。虽然已充分阐明将葡萄糖浓度降低与胰高血糖素释放增加联系起来的电生理过程，但葡萄糖传感器的身份和功能的证据仍不完整。在本研究中，我们旨在解决两个未解决的问题：（1）单个α细胞是否具有通过葡萄糖调节胰高血糖素分泌的内在能力，以及（2）在这种情况下，葡萄糖激酶是否是α细胞的葡萄糖传感器。单细胞 RT-PCR 用于证实葡萄糖激酶是大鼠胰腺α细胞中主要的葡萄糖磷酸化酶。通过 TIRF 显微镜分别测量药理学激活剂和抑制剂对葡萄糖激酶活性的调节，导致单个α细胞释放胰高血糖素的葡萄糖阈值降低或升高。葡萄糖激酶表达的敲低导致葡萄糖对胰高血糖素分泌的控制丧失。总之，这项研究为葡萄糖激酶在大鼠α细胞中胰高血糖素释放的固有葡萄糖调节中发挥关键作用提供了证据。
