CLEC11A improves insulin secretion and promotes cell proliferation in human beta-cells

Beta-cell dysfunction is a hallmark of disease progression in patients with diabetes. Research has been focused on maintaining and restoring beta-cell function during diabetes development. The aims of this study were to explore th e expression of C-type lectin domain containing 11A (CLEC11A), a secreted sulphated glycoprotein, in human islets and to evaluate the effects of CLEC11A on beta-cell funct ion and proliferation in vitro. To test these hypotheses, human islets and human EndoC-beta H1 cell line were used in this study. We identified that CLEC11A was expressed in beta-cells and alpha-cells in human islets but not in EndoC-beta H1 cells, whereas the receptor of CLEC11A called integrin subunit alpha 11 was found in both human islets and En doC-beta H1 cells. Long-term treatment with exogenous recombinant human CLEC11A (rhCLEC11A) accentuated glucose-stimulated insulin secretion, insulin content, and proliferation from human islets and EndoC-beta H1 cells, which was partially due to the accentuated expression levels of transcription factors MAFA and PDX1. However, the impaired beta-cell function and reduced mRNA expression of INS and MAFA in EndoC-beta H1 cells that were caused by chronic palmitate exposure could only be partially improved by the introduction of rhCLEC11A. Based on these results, we conclude that rhCLEC11A promotes insulin secretion, insulin content, and proliferation in human beta-cells, which are associated with the accentuated expression levels of transcription factors MAFA and PDX1. CLEC11A, therefore, may provide a novel therapeutic target for maintaining beta-cell function in patients with diabetes.

Automated summary

This study aimed to explore the expression of C-type lectin domain containing 11A (CLEC11A) in human islets and its effects on beta-cell function and proliferation. It was found that CLEC11A was expressed in beta-cells and alpha-cells in human islets, and its introduction enhanced glucose-stimulated insulin secretion, insulin content, and proliferation in both human islets and EndoC-beta H1 cells. However, its improvement on impaired beta-cell function caused by chronic palmitate exposure was only partial. Based on these findings, CLEC11A may serve as a potential therapeutic target for maintaining beta-cell function in patients with diabetes.