Christiane Ferran MD, PhD
My laboratory has been involved in the fields of islet transplantation and vascular complications of diabetes. Based on unexpected recent results we developed an interest in exploring a novel insulin-independent anti-diabetic function of A20/TNFAIP3, an ubiquitin-editing and NF-kB inhibitory protein that has been the focus of my lab research for the last 20 years. We ave evidence that overexpression of A20 in the liver of streptozotocin-treated diabetic mice normalizes glycemia glycemia and GTT by decreasing hepatic gluconeogenesis and increasing peripheral glucose uptake and glycogen storage. The molecular basis of this novel function of A20, as a positive regulator of glucose metabolism, likely relies on A20-induced modulation of liver-produced anti- vs. pro-diabetic solute carrier proteins (SLC) in a way that favors production and secretion of anti-diabetic (Lipocalin-13/LCN13), and reduces that of pro-diabetic Retinol binding protein 4/RBP4) SLC.