Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, 1580 NW 10(th) Avenue, Miami, FL 33136, USA; Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA; The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm 17177, Sweden.
Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Cell Metab. 2018 Mar 6;27(3):549-558.e4. doi: 10.1016/j.cmet.2018.01.015.
Every animal species has a signature blood glucose level or glycemic set point. These set points are different, and the normal glycemic levels (normoglycemia) of one species would be life threatening for other species. Mouse normoglycemia can be considered diabetic for humans. The biological determinants of the glycemic set point remain unclear. Here we show that the pancreatic islet imposes its glycemic set point on the organism, making it the bona fide glucostat in the body. Moreover, and in contrast to rodent islets, glucagon input from the alpha cell to the insulin-secreting beta cell is necessary to fine-tune the distinctive human set point. These findings affect transplantation and regenerative approaches to treat diabetes because restoring normoglycemia may require more than replacing only the beta cells. Furthermore, therapeutic strategies using glucagon receptor antagonists as hypoglycemic agents need to be reassessed, as they may reset the overall glucostat in the organism.
每种动物物种都有其标志性的血糖水平或血糖设定点。这些设定点不同，一种物种的正常血糖水平（血糖正常）对其他物种来说可能是致命的。小鼠的血糖正常可被认为是人类的糖尿病。血糖设定点的生物学决定因素仍不清楚。在这里，我们表明胰岛对机体施加其血糖设定点，使其成为体内真正的葡萄糖稳态器官。此外，与啮齿动物胰岛不同，来自α细胞的胰高血糖素输入到胰岛素分泌β细胞对于微调独特的人类设定点是必要的。这些发现影响到治疗糖尿病的移植和再生方法，因为恢复血糖正常可能需要不仅仅是替换β细胞。此外，使用胰高血糖素受体拮抗剂作为降血糖药物的治疗策略需要重新评估，因为它们可能会重置机体的整体葡萄糖稳态器官。
