胞质pH值是胰腺β细胞中胰岛素加工和分泌的环境信号纽带，这一成果由同济大学Xiaoqing Zhang、Ling Liu、Yujiang Fang小组经过不懈努力而取得。2024年3月20日出版的《细胞-代谢》杂志发表了这项成果。

研究人员发现当葡萄糖刺激β细胞时，β细胞的细胞膜pH值（pHc）会升高，Smad5可通过其核胞质穿梭感应到该变化。如果β细胞中Smad5发生病变，就会因胰岛素加工和分泌不足而导致高血糖和葡萄糖不耐受。Smad5在调节胰岛素加工和分泌中的作用，是通过调节V-ATP酶活性实现颗粒酸化这一非典型功能完成。

对Smad5基因进行突变或给予碱性水造成细胞膜碱化，可改善高脂饮食（HFD）小鼠产生的葡萄糖不耐受症。总之，该研究结果表明，pHc是连接环境线索与β细胞中胰岛素加工和分泌的直接纽带。

据介绍，胰腺β细胞通过调节胰岛素的加工和分泌对葡萄糖波动进行调控。然而，尚不清楚这一过程是如何在多变的微环境和β细胞内在状态下进行，以及其功能障碍是否与代谢性疾病有关。

附：英文原文

Title: Cytosolic pH is a direct nexus in linking environmental cues with insulin processing and secretion in pancreatic β cells

Author: Yujiang Fang, Hexi Feng, Bowen Zhang, Shuwei Zhang, Yanjie Zhou, Pengcheng Hao, Zhongshu Zhou, Shanshan Zhou, Nan Li, Yi Hui, Lin Ma, Jie Xiong, Jinjin Wu, Ling Liu, Xiaoqing Zhang

Issue&Volume: 2024-03-20

Abstract: Pancreatic β cells actively respond to glucose fluctuations through regulating insulinprocessing and secretion. However, how this process is elaborately tuned in circumstanceof variable microenvironments as well as β cell-intrinsic states and whether its dysfunctionlinks to metabolic diseases remain largely elusive. Here, we show that the cytosolicpH (pHc) in β cells is increased upon glucose challenge, which can be sensed by Smad5via its nucleocytoplasmic shuttling. Lesion of Smad5 in β cells results in hyperglycemiaand glucose intolerance due to insulin processing and secretion deficiency. The roleof Smad5 in regulating insulin processing and secretion attributes to its non-canonicalfunction by regulating V-ATPase activity for granule acidification. Genetic mutationof Smad5 or administration of alkaline water to mirror cytosolic alkalization amelioratedglucose intolerance in high-fat diet (HFD)-treated mice. Collectively, our findingssuggest that pHc is a direct nexus in linking environmental cues with insulin processingand secretion in β cells.

DOI: 10.1016/j.cmet.2024.02.012

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00059-7