It is possible that cancer cells and/or the surrounding stromal cells, specifically PSCs (the key producers of the collagenous stroma of PDAC), secrete factor(s) that act via a ‘humoral’ pathway to (i) inhibit islet cell function at a distance from the PanINs or cancer foci and/or (ii) affect insulin signalling pathways leading to insulin resistance. Here, INS is linked to cancer.