HPSE and diabetes mellitus: Here we report that in the context of hyperinsulinemic conditions [a common phenomenon in PDAC, either in the setting of new onset or long-standing diabetes (Permert et al., 1993; Permert et al., 1997; Stolzenberg-Solomon et al., 2005; Sah et al., 2013)], heparanase augments insulin-INSR signaling cascade in pancreatic tumor cells.