2030-LB: Matairesinol and Its Metabolite Enterolactone Promote Glucose Uptake in 3T3-L1 Adipocytes via a Glut4/Akt-Dependent Mechanism

Type-2 diabetes (T2D) is marked by dysregulated glucose homeostasis resulting in chronic fasting hyperglycemia and insulin resistance. Previous studies indicate that habitual coffee consumption is negatively correlated with the development of T2D. Matairesinol (MA) is a low molecular weight polyphenol that is found in coffee. MA and its gut microbial metabolite, enterolactone (ENL), have previously been shown to elicit anti-diabetic properties in studies analyzing skeletal muscle. However, their effects have not been demonstrated in adipocytes. In this study, 3T3-L1 adipocytes were treated with either MA or ENL in a dose-dependent manner and subsequently assayed for glucose uptake efficacy. We found that 1 and 10 µM ENL as well as 10, 15, 50, and 100 µM MA significantly increased glucose uptake in 3T3-L1 adipocytes compared to the vehicle. We also demonstrated that both MA- and ENL-stimulated glucose uptake were blunted by selective chemical inhibitors of Glut4, but not Glut1, thus indicating a potential Glut4-dependent mechanism. In addition, we show that ENL (50 µM) significantly increases Akt phosphorylation compared to the vehicle and to an extent that is statistically indistinguishable from the effects of insulin. Our data indicate that these compounds work through an Akt/Glut4-dependent mechanism thus warranting continued investigation into the molecular mechanisms by which they promote glucose uptake.