Importance of cell-matrix interactions in rat islet β-cell secretion in vitro: Role of α6β1 integrin

Abstract

It has long been recognized that islet cell function is rapidly altered in vitro, but can be maintained, at least in part, when cells are layered on defined extracellular matrices. The present work addresses the influence of short-term cell-matrix interactions on islet β-cell function and provides first insight into the molecular basis of these interactions. When primary rat β-cells were allowed to attach to a matrix produced by a rat carcinoma cell line (804G), there was an increased insulin secretory response to secretagogues. This change was the result of an increase in the proportion of actively secreting β-cells and in the amount of insulin secreted per active cell, as shown using the reverse hemolytic plaque assay. In turn, the spreading or flattening of β-cells on this matrix was enhanced by secretagogues, and flattened cells secreted more insulin than rounded cells. Using indirect immunofluorescence, it was found that 1) α6β1 integrins are present at the surface of islet cells in situ, 2) α6β1 expression is heterogeneous among purified β-cells and is upregulated by insulin secretagogues, 3) α6β1 expression is higher in spreading cells, and 4) anti-α6β1-specific antibodies decrease spreading. These observations demonstrate that islet cell-matrix interactions can improve the sensitivity of insulin cells to glucose and are mediated, at least in part, by α6β1 integrins, suggesting that outside-in signaling through α6β1 integrin plays a major role in the regulation of β-cell function.