Identification of SEC16B as a novel regulator of glucose homeostasis – Published online 24/07/2025

Ruo-Xin Zhang, An-Qi Li, Xin-Yuan Zhao, Bei Wang, Zhi-Can Yang, Zhi-Ying Liu, Chen Ji, Yan-Chuan Shi, G. Gregory Neely & Qiao-Ping Wang

Genome-wide association studies (GWAS) have linked SEC16 homologue B (SEC16B) to obesity and type 2 diabetes risk, yet its specific role in glucose regulation remains elusive. In this issue, Zhang et al (https://doi.org/10.1007/s00125-025-06501-8) present research combining Drosophila genetics and murine models, demonstrating that SEC16B deficiency triggers glucose intolerance in both species. Mechanistically, loss of SEC16B impairs beta cell function by downregulating cholinergic signalling and disrupting intracellular calcium dynamics, ultimately compromising insulin secretion. The authors discuss how these findings fill a key knowledge gap by directly connecting this GWAS-identified risk locus to specific insulin secretory defects. They conclude that the identification of SEC16B’s role in cholinergic-driven calcium influx offers a novel therapeutic target for restoring glycaemic control in type 2 diabetes and metabolic disorders.

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