The effect of duodenal-jejunal bypass on glucose-dependent insulinotropic polypeptide secretion in Wistar rats

Abstract

Background: Enteroendocrine K cells secrete the incretin hormone glucose-dependent insulinotropic peptide (GIP) and are predominately located in the duodenum. GIP levels should decrease after gastric bypass due to duodenal exclusion; however, studies have found conflicting data regarding the changes in GIP secretion after gastric bypass and duodenal-jejunal bypass (DJB).

Methods: We performed a DJB or Sham surgery on Wistar rats followed by an oral glucose tolerance test on postoperative (post-op) day 12 and superior mesenteric lymphatic cannulation on post-op day 14. We measured meal-stimulated GIP concentrations and small bowel GIP and GLP-1 protein content after DJB or Sham surgery.

Results: There was no difference in glucose tolerance by 12 days post-op. We found no difference in lymphatic GIP concentration area under the curve between DJB and Sham rats (15,240 pg/ml min +/- 2,651 vs. 17,201 pg/ml min +/- 2,763, respectively, p = 0.62). GIP and GLP-1 protein contents were both significantly increased only in the midjejunum in DJB rats compared to Sham rats (p = 0.009 and p = 0.01, respectively).

Conclusions: Plasma and lymphatic GIP concentrations did not significantly change after DJB in Wistar rats. DJB increased GIP protein content in the midjejunum at the new site of nutrient absorption, but this was surprisingly not countered by a decrease in GIP protein content in the bypassed duodenum. Further studies are needed to determine the mechanisms that account for the discrepancy in GIP production and subsequent secretion after DJB as well as what role GIP plays in the effect of gastrointestinal surgery on glucose homeostasis.

Fig. 1

Body weight and food intake after gastrointestinal surgery in Wistar rats. Body weights (a) and food intake (b) were assessed daily preoperatively and for 2 weeks postoperatively. *p<0.05, statistically different between the two surgical groups. Data are presented as mean±SE

Fig. 2

An oral glucose tolerance test (2 g/kg D-glucose) was performed 12 days after DJB or Sham surgery. Plasma glucose concentrations (a) and insulin concentrations (c) were measured at fasting and 15, 30, 60, and 120 min after the glucose gavage. Glucose concentration AUC (b) and insulin concentration AUC (d) were determined using the trapezoidal rule. Data are presented as mean±SE

Fig. 3

Total GIP concentrations were measured from plasma or gastrointestinal lymph (a) at fasting and for 1 h following the administration of a mixed meal (7.68 ml/kg Ensure). Plasma and lymphatic GIP concentration AUC (b) was calculated using the trapezoidal rule. Data are presented as mean±SE

Fig. 4

Percentage intestinal GIP (a) or GLP-1 protein content (b) was determined at 2 weeks after DJB or Sham surgery in Wistar rats. Intestinal segments were taken from the duodenum, proximal jejunum (distal to the duodenojejunostomy in DJB rats or 10 cm distal to the ligament of Treitz in Sham rats), midjejunum (distal to the jejujejunostomy in DJB rats or 25 cm distal to the ligament of Treitz in Sham rats), and distal ileum. *p<0.05, statistically different for the tested segment of small bowel between DJB and Sham rats. Data are presented as mean±SE