Rather we were intrigued by recent reports indicating that NE released by degranulation can have profound effects on surrounding tissues (36, 37). In the first of these pivotal reports, it was shown that exogenously liberated NE uncoupled tumor cell signaling via the degradation of IRS1, leading to deregulated proliferation (36). This was extended upon in a murine diabetes model where it was shown that exogenous NE led to insulin resistance in hepatocytes and contributed to inflammation-induced metabolic disease (37).