Duodenal-Jejunal Bypass and Jejunectomy Improve Insulin Sensitivity in Goto-Kakizaki Diabetic Rats Without Changes in Incretins or Insulin Secretion

Abstract

Gastric bypass surgery can dramatically improve type 2 diabetes. It has been hypothesized that by excluding duodenum and jejunum from nutrient transit, this procedure may reduce putative signals from the proximal intestine that negatively influence insulin sensitivity (SI). To test this hypothesis, resection or bypass of different intestinal segments were performed in diabetic Goto-Kakizaki and Wistar rats. Rats were randomly assigned to five groups: duodenal-jejunal bypass (DJB), jejunal resection (jejunectomy), ileal resection (ileectomy), pair-fed sham-operated, and nonoperated controls. Oral glucose tolerance test was performed within 2 weeks after surgery. Baseline and poststimulation levels of glucose, insulin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured. Minimal model analysis was used to assess SI. SI improved after DJB (SI = 1.14 ± 0.32 × 10−4 min−1 ⋅ pM−1) and jejunectomy (SI = 0.80 ± 0.14 × 10−4 min−1 ⋅ pM−1), but not after ileectomy or sham operation/pair feeding in diabetic rats. Both DJB and jejunal resection normalized SI in diabetic rats as shown by SI levels equivalent to those of Wistar rats (SI = 1.01 ± 0.06 × 10−4 min−1 ⋅ pM−1; P = NS). Glucose effectiveness did not change after operations in any group. While ileectomy increased plasma GIP levels, no changes in GIP or GLP-1 were observed after DJB and jejunectomy. These findings support the hypothesis that anatomic alterations of the proximal small bowel may reduce factors associated with negative influence on SI, therefore contributing to the control of diabetes after gastric bypass surgery.