Ricerc@Sapienza

Insulin resistance (i.r.), a condition defined as a relative inability of body tissues to respond to the action of insulin, is one of the main culprits in the association between obesity, particularly visceral, and metabolic diseases such as type 2 diabetes mellitus (T2DM). In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, proinflammatory cytokines and other factors that are involved in the development of i.r.. However, despite these association have been proved, the exact mechanisms promoting the onset of i.r. are still unclear.
During the last years, biliverdin reductase-A (BVR-A) emerged as a novel mediator of the insulin signaling machinery, possibly involved in the regulation glucose uptake. In that frame, it has been demonstrated that other than its canonical activity in the degradation pathway of heme, BVR-A is a direct target of the insulin receptor (IR) similar to IRS1. Once activated by insulin, IR promotes the phosphorylation of BVR-A on specific Tyr residues, which leads to the activation of BVR-A as a unique Ser/Thr/Tyr kinase. Through this kinase activity BVR-A regulate the insulin signaling at different levels. It is an upstream regulator of IRS1, as well as a downstream regulator of both Akt and MAPK activation. These features make the protein of great interest in the contest of the comprehension of insulin signaling defects.
The aim of this project will be the characterization of the role of BVR-A in the onset of i.r. in lymphocytes collected from obese (Ob) and obese who develope diabetes (Ob/T2DM) before and after bariatric surgery, this latter known to cause significant long-term loss of weight and recovery from T2DM.
This knowledge will be fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention.