Glucose homeostasis is maintained through organ crosstalk that regulates secretion of insulin to keep blood glucose levels within a physiological range. In type 2 diabetes, this coordinated response is altered, leading to a deregulation of beta cell function and inadequate insulin secretion. Reprogramming of white adipose tissue has a central role in this deregulation, but the critical regulatory components remain unclear. Here, we demonstrate that expression of the transcriptional coregulator GPS2 in white adipose tissue is correlated with insulin secretion rate in humans. The causality of this relationship is confirmed using adipocyte-specific GPS2 knockout mice, in which inappropriate secretion of insulin promotes glucose intolerance. This phenotype is driven by adipose-tissue-secreted factors, which cause increased pancreatic islet inflammation and impaired beta cell function. Thus, our study suggests that, in mice and in humans, GPS2 controls the reprogramming of white adipocytes to influence pancreatic islet function and insulin secretion.

通过调节胰岛素分泌以使血糖水平保持在生理范围内的器官串扰来维持葡萄糖稳态。在2型糖尿病中，这种协同反应发生改变，导致β细胞功能失调和胰岛素分泌不足。白色脂肪组织的重编程在这种放松调节中起着核心作用，但是关键的调节成分仍然不清楚。在这里，我们证明了转录脂肪调节剂GPS2在白色脂肪组织中的表达与人类胰岛素的分泌速率相关。使用脂肪细胞特异性GPS2基因敲除小鼠证实了这种关系的因果关系，其中不适当的胰岛素分泌促进了葡萄糖耐受不良。这种表型是由脂肪组织分泌因子驱动的，会导致胰岛炎症增加和β细胞功能受损。因此，我们的研究表明，在小鼠和人类中，GPS2控制着白色脂肪细胞的重编程以影响胰岛功能和胰岛素分泌。