Importance of cell-matrix interactions in rat islet beta-cell secretion invitro - Role of alpha 6 beta 1 integrin

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 d efined extracellular matrices. The present work addresses the influence of short-term cell-matrix interactions on islet beta-cell function and provide s first insight into the molecular basis of these interactions. When primar y rat beta-cells were allowed to attach to a matrix produced by a rat carci noma 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 beta-cells and in the amount of insulin secreted per active cell, as shown using the reverse hemolytic plaque assay. In turn, t he spreading or flattening of beta-cells on this matrix was enhanced by sec retagogues, and flattened cells secreted more insulin than rounded cells. U sing indirect immunofluorescence, it was found that 1) alpha 6 beta 1 integ rins are present at the surface of islet cells in situ, 2) alpha 6 beta 1 e xpression is heterogeneous among purified beta-cells and is upregulated by insulin secretagogues, 3) alpha 6 beta 1 expression is higher in spreading cells, and 4) anti-alpha 6 beta 1-specific antibodies decrease spreading. T hese observations demonstrate that islet cell-matrix interactions can impro ve the sensitivity of insulin cells to glucose and are mediated, at least i n part, by alpha 6 beta 1 integrins, suggesting that outside-in signaling t hrough alpha 6 beta 1 integrin plays a major role in the regulation of beta -cell function.