Bypassing the duodenum does not improve insulin resistance associated with diet-induced obesity in rodents

Roux-en-y gastric bypass (RYGB) surgery rapidly improves glucose tolerance and reverses insulin resistance in obese patients. It has been hypothesized that this effect is mediated by the diversion of nutrients from the proximal small intestine. We utilized duodenal-jejunal bypass (DJB) as a modification of gastric bypass to determine the effect of nutrient diversion from the foregut without gastric restriction on insulin resistance in obese rats. The effects of DJB or Sham surgery on glucose homeostasis were determined in both high-fat-fed Long-Evans and Wistar rats. Body weight and food intake were measured weekly postoperatively, and body composition was monitored before and after surgery. Glucose tolerance was tested before and as early as 1 month postoperation; additionally, in Wistar rats, insulin sensitivity was determined by a hyperinsulinemic-euglycemic clamp (HIEC). DJB did not affect body weight, body composition, glucose tolerance, or insulin concentrations over the period of the study. The average glucose infusion rate (GIR) during the HIEC was 6.2 ± 1.16 mg/kg/min for Sham rats compared to 7.2 ± 1.71 mg/kg/min for DJB rats (P = 0.62), and neither endogenous glucose production (EGP; P = 0.81) nor glucose utilization (glucose disappearance (R(d)), P = 0.59) differed between DJB and Sham rats. DJB does not affect insulin resistance induced by a high-fat diet in Long-Evans and Wistar rats. These data suggest that duodenal bypass alone is an insufficient mechanism to alter insulin sensitivity independent of weight loss in obese, nondiabetic rodents.