Pericytes contribute to the islet basement membranes to promote beta-cell gene expression

beta -Cells depend on the islet basement membrane (BM). While some islet BM components are produced by endothelial cells (ECs), the source of others remains unknown. Pancreatic pericytes directly support beta -cells through mostly unidentified secreted factors. Thus, we hypothesized that pericytes regulate beta -cells through the production of BM components. Here, we show that pericytes produce multiple components of the mouse pancreatic and islet interstitial and BM matrices. Several of the pericyte-produced ECM components were previously implicated in beta -cell physiology, including collagen IV, laminins, proteoglycans, fibronectin, nidogen, and hyaluronan. Compared to ECs, pancreatic pericytes produce significantly higher levels of alpha 2 and alpha 4 laminin chains, which constitute the peri-islet and vascular BM. We further found that the pericytic laminin isoforms differentially regulate mouse beta -cells. Whereas alpha 2 laminins promoted islet cell clustering, they did not affect gene expression. In contrast, culturing on Laminin-421 induced the expression of beta -cell genes, including Ins1, MafA, and Glut2, and significantly improved glucose-stimulated insulin secretion. Thus, alongside ECs, pericytes are a significant source of the islet BM, which is essential for proper beta -cell function.

Automated summary

Pericytes produce multiple components of the pancreatic and islet BM matrices, including laminins that regulate beta-cell function. The findings suggest that pericytes play a significant role in supporting beta-cells and insulin secretion in the islets.