2. Academic Validation
  3. Osmosensor TMEM63B facilitates insulin secretion in pancreatic β-cells

Osmosensor TMEM63B facilitates insulin secretion in pancreatic β-cells

  • Sci China Life Sci. 2025 Feb 20. doi: 10.1007/s11427-024-2833-3.
Jing-Jing Tu # 1 2 3,  Chang Ye # 1 3,  Xiao-Yu Teng # 2,  Yan-Yu Zang 3,  Xiao-Ye Sun 4,  Shuai Chen 5,  Jiang Chen 6,  Yun Stone Shi 7 8 9
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
  • 2 Guangdong Institute of Intelligence Science and Technology, Zhuhai, 519031, China.
  • 3 Ministry of Education Key Laboratory of Model Animal for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, Medical School, Nanjing University, Nanjing, 210032, China.
  • 4 Department of Hepatology and Gastroenterology, Tianjin First Central Hospital, Tianjin, 300192, China.
  • 5 Ministry of Education Key Laboratory of Model Animal for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, Medical School, Nanjing University, Nanjing, 210032, China. schen6@163.com.
  • 6 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China. chenjiang@nicemice.cn.
  • 7 Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China. shiyun@gdiist.cn.
  • 8 Guangdong Institute of Intelligence Science and Technology, Zhuhai, 519031, China. shiyun@gdiist.cn.
  • 9 Ministry of Education Key Laboratory of Model Animal for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, Medical School, Nanjing University, Nanjing, 210032, China. shiyun@gdiist.cn.
  • # Contributed equally.
PMID: 39985646 DOI: 10.1007/s11427-024-2833-3
Abstract

Elevated glucose metabolism triggers two primary processes that lead to β-cell depolarization and Insulin secretion: the closure of ATP-sensitive K+ channels via ATP-dependent mechanisms and the activation of mechanosensitive channels (MSCs) due to cell swelling. However, the identity of these MSCs remains unclear. In this study, we found that TMEM63B is a stretch-activated cation channel (SAC) crucial for regulating Insulin secretion in response to elevated glucose levels. TMEM63B is abundantly expressed in β-cells, and its deletion impairs Insulin secretion triggered by high glucose. High glucose levels typically increase CA2+ influx and firing frequency in β-cells, a response largely eliminated when TMEM63B is deleted. Mechanistically, glucose metabolism induces cell swelling and activates TMEM63B, which, in turn, leads to β-cell depolarization and Insulin secretion. In conclusion, our findings demonstrate that TMEM63B is an SAC essential for regulating Insulin secretion in response to elevated glucose levels.

Keywords

TMEM63B; high glucose; hypotonicity; insulin secretion; mechanosensitive cation channels; osmosensor; pancreatic β-cells.

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