Duodenal-jejunal bypass and jejunectomy improve insulin sensitivity in Goto-Kakizaki diabetic rats without changes in incretins or insulin secretion

Gastric bypass surgery results in rapid and sustained remission of type 2 diabetes (1,2). Experimental evidence from both animal (3,4) and human studies (5-7) suggest that the improvement of diabetes [...]
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 ([S.sub.1]). 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 [S.sub.1]. [S.sub.1] improved after DJB ([S.sub.1] = 1.14 ± 0.32 x [10.sup.-4] [min.sup.-1] x [pM.sup.-1]) and jejunectomy ([S.sub.1] = 0.80 [+ or -] 0.14 x [10.sup.-4] [min.sup.-1] x [pM.sup.-1]), but not after ileectomy or sham operation/pair feeding in diabetic rats. Both DJB and jejunal resection normalized [S.sub.1] in diabetic rats as shown by [S.sub.1] levels equivalent to those of Wistar rats ([S.sub.1] = 1.01 ± 0.06 x [10.sup.-4] [min-sup.-1] x [pM.sup.-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 [S.sub.1] therefore contributing to the control of diabetes after gastric bypass surgery. Diabetes 2014;63:1069-1078 | DOI: 10.2337/db13-0856