Beta-cells rely on the islet microenvironment for their functionality and mass. Pericytes, along with endothelial cells, make up the dense islet capillary network. However, while the role of endothelial cells in supporting beta-cell homeostasis is vastly investigated, the role of pericytes remains largely unknown. Here, we focus on pericytes' contribution to beta-cell function. To this end, we employed a transgenic mouse system that allows Diphtheria Toxin -based depletion of pericytes. Our results indicate that islets depleted of their pericytes have reduced insulin content and expression. Additionally, isolated islets displayed an impaired glucose-stimulated insulin secretion, accompanied by a reduced expression of genes associated with beta-cell function. Importantly, reduced levels of the transcription factors MafA and Pdx1 point to beta-cell dedifferentiation in the absence of pericytes. Ex vivo depletion of pericytes in isolated islets resulted in a similar impairment of gene expression, implicating their direct, blood-flow independent role in maintaining beta-cell maturity. To conclude, our findings suggest that pericytes are pivotal components of the islet niche, which are required for beta-cell maturity and functionality. Abnormalities of islet pericytes, as implicated in type 2 diabetes, may therefore contribute to beta-cell dysfunction and disease progression.
- Received March 21, 2016.
- Accepted July 1, 2016.
- © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.