Role of collagen type III / ITGB1 signalling in stellate cell‐mediated regulation of β‐cell survival and insulin secretion in the pancreatic islet microenvironment

AIMS: The effects of various cells in the pancreatic islet microenvironment on the function of β-cells remain at the forefront of current islet-related research. Our previous study identified that islet stellate cells (ISCs) exist in the islet microenvironment, expressing type III collagen and enhancing insulin secretion from co-cultured β-cells. However, the mechanism by which they regulate insulin secretion in neighbouring β-cells via type III collagen remains unclear. METHODS: This study combined in vivo and in vitro approaches, utilising immunohistochemistry to assess protein expression, flow cytometry for apoptosis detection and Western blotting to measure the expression levels of signalling molecules downstream of the Integrin β1 (ITGB1)/Focal Adhesion Kinase (FAK) pathway. Additionally, the antiapoptotic effects of collagen type III were evaluated using caspase 3/7 assays. RESULTS: In vitro experiments demonstrated that collagen type III inhibits β-cell apoptosis, promotes insulin secretion and enhances the survival of co-cultured MIN6 β-cells through the ITGB1 receptor. This effect is mediated by the activation of the collagen type III/FAK/Src, Forkhead Box O1 (FOXO1)/Pancreatic Duodenal Homeobox-1 (PDX1) signalling pathway in an integrin β1-dependent manner. CONCLUSIONS: ISCs reduce β-cell apoptosis and enhance insulin secretion through the collagen type III/Integrin β1 (ITGB1) system, revealing a new mechanism by which stellate cells regulate neighbouring β-cell function in the islet microenvironment.