Mechanisms underlying the remission of T2DM following RYGB Surgery Grant uri icon

abstract

  • The incidence of Type 2 diabetes (T2D) has grown at a dramatic rate and is increasing towards epidemic proportions in the US, with an incidence of nearly 10%. Cardiovascular disease is the leading cause of death (65%) in individuals with T2D due to hyperglycemia and hyperinsulinemia, which is associated with defective glucose oxidation in peripheral tissues (i.e. skeletal muscle). Remarkably, Roux-en-Y gastric bypass (RYGB) surgery has been demonstrated to rapidly improve glucose oxidation and resolve T2D before substantial weight loss occurs, which in turn is retained over a long term. Despite these striking observations, the underlying mechanisms responsible for the rapid as well as long-term improvements remain unclear, and likely involve skeletal muscle as it is the major site of glucose oxidation. Although several mechanisms have been proposed, it is still unclear whether the improvement of glucose oxidation after RYGB surgery are due to the alterations in the intrinsic metabolic phenotype of skeletal muscle, the release of systemic factor(s), or a combination of both. In our lab, we have the unique capacity to dissect out these potential mechanisms by examining the metabolic characteristics of human skeletal muscle cells (HSkMCs) that are influenced genetically or epigenetically. Taken together, our central hypothesis of the current proposal is that early alteration of systemic factor(s) along with long-term alteration of intrinsic metabolic phenotypes of the HSkMCs are responsible for the restoration of defective skeletal muscle glucose oxidation associated with T2D after RYGB surgery. The long-term goal of this research is to determine the mechanisms underlying the remission of T2D following RYGB that will result in potential novel therapeutic approaches to treat T2D.

date/time interval

  • July 2015 - June 2017