Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat

Abstract

The hindgut hypothesis posits improvements in Type 2 diabetes after gastric bypass surgery are due to enhanced delivery of undigested nutrients to the ileum, which increase incretin production and insulin sensitivity. The present study investigates the effect of ileal interposition (IT), surgically relocating a segment of distal ileum to the proximal jejunum, on glucose tolerance, insulin sensitivity, and glucose transport in the obese Zucker rat. Two groups of obese Zucker rats were studied: IT and sham surgery ad libitum fed (controls). Changes in food intake, body weight and composition, glucose tolerance, insulin sensitivity and tissue glucose uptake, and insulin signaling as well as plasma concentrations of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide were measured. The IT procedure did not significantly alter food intake, body weight, or composition. Obese Zucker rats demonstrated improved glucose tolerance 3 wk after IT compared with the control group (P < 0.05). Euglycemic, hyperinsulinemic clamp and 1-[(14)C]-2-deoxyglucose tracer studies indicate that IT improves whole body glucose disposal, insulin-stimulated glucose uptake, and the ratio of phospho- to total Akt (P < 0.01 vs. control) in striated muscle. After oral glucose, the plasma concentration of glucagon-like peptide-1 was increased, whereas GIP was decreased following IT. Enhanced nutrient delivery to the ileum after IT improves glucose tolerance, insulin sensitivity and muscle glucose uptake without altering food intake, body weight, or composition. These findings support the concept that anatomic and endocrine alterations in gut function play a role in the improvements in glucose homeostasis after the IT procedure.

Ileal Transposition Decreases Plasma Lipopolysaccharide Levels in Association with Increased L Cell Secretion in Non-obese Non-diabetic Rats

“…In this study, we reproducibly observed the reported effects of IT surgery in rodents: improved insulin sensitivity [31], increased L cell secretion including GLP-1 and PYY [14,32], and histological adaptation of the small intestine [32]. In addition, for the first time, we observed that circulating LPS levels decreased after IT surgery even though the surgery was performed in a non-diabetic non-obese rat model fed a normal chow diet.…”

“…In some studies with genetically obese rodent models, IT did not elicit a significant weight loss until 4 weeks [48] or 8 weeks [31] after the surgery. Notably, in our study, IT exhibited a biphasic response in food intake: an early decrease followed by a gradual recovery, which was also observed by other researchers [32,47].…”

Effects of sleeve gastrectomy and ileal transposition, alone and in combination, on food intake, body weight, gut hormones, and glucose metabolism in rats

“…Other important factors contributing to variation in these effects are the variable lengths of transposed segment and the insertion site of ileal segments. For instance, transposing a 5-10 cm of ileal segment did not have a significant impact on food intake and weight gain (38,41,43,44,117,118,120) whereas a 20-cm segment decreased intake and weight gain (20,39). SGIT is a new emerging surgical technique involving combination of SG and IT surgery in one subject (126).…”

Ileal transposition in surgical treatment for type 2 diabetes mellitus

“…С другой стороны, пролиферация β-клеток в островках поджелудочной железы после ИТ была Диагностика, контроль и лечение подтверждена иммуногистохимическими методами [31]. Кроме того, показано повышение потребления тканями глюкозы после ИТ [32]. Выполнение ИТ повышало уровень экспрессии мРНК инсулинозависимого транспортера глю-козы GLUT4 в скелетной мускулатуре и жировой ткани [24].…”