Circulating betatrophin is increased in type 2 and gestational diabetes mellitus

Objective: Betatrophin has recently been introduced as a novel adipokine/hepatokine which promotes pancreatic β cell proliferation and improves glucose tolerance in several mouse models of insulin resistance. However, regulation of betatrophin in subjects with diabetes mellitus in vivo and in adipocytes in vitro has not been thoroughly determined. Design and Methods: Circulating betatrophin was quantified by ELISA in patients with type 2 diabetes mellitus (T2DM) and in women with gestational diabetes mellitus (GDM) as compared to controls. Moreover, the effects of insulin resistance-inducing hormones and differentiation on betatrophin mRNA production in 3T3-L1 adipocytes were investigated in vitro. Results: Median [interquartile range] serum betatrophin levels were higher in patients with T2DM (1.19 [0.37] µg/l) as compared with nondiabetic subjects (1.03 [0.47] µg/l) (P = 0.005). Furthermore, median serum betatrophin levels were higher in women with GDM (1.79 [0.53] µg/l) as compared to non-diabetic gestational age-matched controls (1.58 [0.44] µg/l) (P = 0.002). Moreover, betatrophin mRNA expression was significantly induced by insulin and during adipogenesis in 3T3-L1 adipocytes in vitro whereas its synthesis was not influenced by interleukin-6, interleukin-1β, isoproterenol, dexamethasone, and growth hormone. Conclusions: Circulating betatrophin is increased in T2DM and GDM in vivo. Insulin-induced betatrophin mRNA expression in adipocytes might contribute to this effect. Further studies need to elucidate the pathophysiological significance of betatrophin upregulation in T2DM and GDM.