Project Summary/Abstract Type 2 diabetes mellitus (T2DM) associated with obesity can now be successfully treated by bariatric surgery. The metabolic effect is rapid ? in part independent of the effect on weight loss ? and mediated by gut factors. We are exploring the possibility that this beneficial effect on T2DM can be achieved without major surgery by creating a small side-to-side magnetic compression anastomosis between the duodenum and the ileum (Magnetic Duodenal-Ileal Bypass, or ?DIPASS?). Our preliminary data in mini-pigs suggest that, by diverting a small amount of digestive juices (gastric, biliary, pancreatic) to the ileal mucosa, this intestinal short cut is able to mimic the beneficial metabolic and hormonal effect of bypass surgeries on glucose metabolism. This proposal will test: 1) the feasibility of inserting the intestinal short cut (DIPASS) in a non-human primate model of metabolic syndrome; 2) the efficacy of the DIPASS procedure, versus sham operation, on improving metabolism; and 3) the mechanism by which DIPASS exerts its effect on glucose metabolism. We will also collect a unique biobank of tissue samples that will allow further studies to assess the molecular mechanism by which the procedure exerts its effect. DIPASS can be accomplished minimally invasively as an outpatient procedure using our previously developed magnetic anastomosis device (?Magnamosis?) and newly developed trans-oral delivery devices that enable an incisionless procedure. Data generated from this proposal will have direct translational application and will enable us to develop future studies in humans.