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Metallothionein 1 negatively regulates glucose-stimulated insulin secretion and is differentially expressed in conditions of beta cell compensation and failure in mice and humans – published online 17/10/2019

Fig from Bensallem paper

Mohammed Bensellam, Yan-Chuan Shi, Jeng Yie Chan, D. Ross Laybutt, Heeyoung Chae, Michel Abou-Samra, Evan G. Pappas, Helen E. Thomas, Patrick Gilon, Jean-Christophe Jonas

The mechanisms of beta cell adaptation to insulin resistance in obesity and of beta cell failure in type 2 diabetes are poorly defined. Several metallothionein genes are upregulated in islets from type 2 diabetic donors, but their role in beta cells is unclear. In this issue, Bensellam et al ( report that beta cell compensation in murine models of obesity correlates with downregulation of islet metallothionein 1 (Mt1) and Mt2 gene expression, while beta cell failure correlates with their upregulation. They also confirm that MT1X expression is upregulated in islets isolated from type 2 diabetic donors. Combining in vivo, ex vivo and in vitro complementary approaches, the authors demonstrate that Mt1 inhibition enhances glucose-stimulated insulin secretion and improves glucose tolerance, whereas its overexpression attenuates the secretory response. They conclude that MT1 negatively regulates beta cell function and propose that MT1 inhibition may represent a potential strategy to enhance insulin secretion in (pre)diabetes.

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