The Entire Small Intestine Mediates the Changes in Glucose Homeostasis After Intestinal Surgery in Goto-Kakizaki Rats

Abstract

To investigate the potential interaction between excluding foregut and interposing hindgut and the role of different portions of the small intestine in mediating changes in some glucoregulatory mechanisms and glucose homeostasis after intestinal surgery in Goto-Kakizaki (GK) rats. Previous studies have revealed changes in glucoregulatory mechanisms and glucose homeostasis after excluding foregut and interposing hindgut alone and lead to the "foregut hypothesis" and "hindgut hypothesis." However, these hypotheses are not mutually exclusive. Duodenal-jejunal bypass (DJB), ileal interposition (IT), duodenal-jejunal bypass with ileal interposition (DJBIT), sub-ileal interposition (sIT), and sham operations were performed on GK rats. Main outcome measures were oral glucose tolerance (studied at 0, 2, 4, 8, and 24 weeks), insulin sensitivity, β-cell function, and postprandial levels of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic peptide(GIP) (evaluated at 2 and 24 weeks). Global body weight in the control group was higher than in the operation groups at postoperative week 2, but it was similar among groups at postoperative week 24. The DJBIT procedure induced synergistic improvement in glucose tolerance and insulin sensitivity (P < 0.05). Generalized linear mixed-model analysis confirmed that glucose tolerance in nonsham operation groups improved over time (P < 0.001), with a significant time × treatment interaction (P < 0.001). Fasting C-peptide, postprandial insulin, GLP-1, and PYY levels increased after nonsham operations (P < 0.05); however, they were not significantly different among the DJBIT, DJB, and IT groups (P > 0.05). Compared with sub-IT, IT induced better glucose tolerance (P < 0.05) and higher postprandial insulin, GLP-1 and PYY levels (P < 0.05), and no significant difference in insulin sensitivity and fasting C-peptide was observed (P > 0.05). None of the surgical procedures affected glucose-stimulated GIP levels (P > 0.05). This study provides experimental evidence that excluding foregut and interposing hindgut provided independent and synergistic changes in glucose homeostasis after intestinal surgery in GK rats and that glucose tolerance improved over time.