Tamoxifen treatment causes early hepatic insulin resistance
Nora Klöting, Matthias Kern, Michele Moruzzi, Michael Stümvoll, Matthias Blüher
Abstract
Tamoxifen is widely used as an effective adjuvant treatment and prevention of estrogen receptor-positive breast cancer [ 1 ]. Tamoxifen decreases food intake, body weight and (at least in the short-term) fat mass in rodents. Despite lowering body weight in obese women, tamoxifen may increase the incidence of diabetes [ 2 ]. This potential side effect has been attributed to decreased β -cell survival and proliferation, but also hepatic steatosis in rodents [ 3 ]. We and others have recently demonstrated that tamoxifen affects glucose, lipid metabolism, transient body composition changes which may originate from tamoxifen-induced adipose tissue necrosis followed by de novo adipocyte recruitment and fat redistribution including fat accumulation in the liver in the longer term [ 3 , 4 ]. Indeed, the development of fatty liver was observed as early as 3 months after initiation of tamoxifen treatment in women with breast cancer [ 5 ]. However, the precise mechanisms of potential diabetogenic effects of tamoxifen are still not entirely clear. Therefore, we aimed to systematically elucidate the development of tamoxifen-related hyperglycemia using the hyperinsulinemic–euglycemic clamps.