Galectin-3 impairs calcium transients and β-cell function
Qian Jiang, Qijin Zhao, Yibing Chen, Chunxiao Ma, Xiaohong Peng, Xi Wu, Xingfeng Liu, Ruo‐Ran Wang, Shaocong Hou, Lijuan Kong, Yanjun Wan, Shusen Wang, Zhuo‐Xian Meng, Bing Cui, Liangyi Chen, Pingping Li
Abstract
In diabetes, macrophages and inflammation are increased in the islets, along with β-cell dysfunction. Here, we demonstrate that galectin-3 (Gal3), mainly produced and secreted by macrophages, is elevated in islets from both high-fat diet (HFD)-fed and diabetic db/db mice. Gal3 acutely reduces glucose-stimulated insulin secretion (GSIS) in β-cell lines and primary islets in mice and humans. Importantly, Gal3 binds to calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and inhibits calcium influx via the cytomembrane and subsequent GSIS. β-Cell CACNG1 deficiency phenocopies Gal3 treatment. Inhibition of Gal3 through either genetic or pharmacologic loss of function improves GSIS and glucose homeostasis in both HFD-fed and db/db mice. All animal findings are applicable to male mice. Here we show a role of Gal3 in pancreatic β-cell dysfunction, and Gal3 could be a therapeutic target for the treatment of type 2 diabetes.