Long segment ileal transposition leads to early amelioration of glucose control in the diabetic obese Zucker rat.

Abstract

IntroductionFast delivery of food to the terminal ileum is thought to be pathophysiologically responsible for type 2 diabetes remission after obesity surgery. Imitating this effect, ileal transposition (IT) is designed as initiating diabetes remission for non-obese patients.AimTo date, it is not clear which length of the transposed segment achieves the best glucose lowering results. As previous rodent data mostly rely on a 10 cm IT, the current study evaluated a long segment IT (20 cm) in the diabetic obese Zucker rat.Material and methodsTwenty male diabetic obese Zucker rats (Crl:ZUC-Leprfa) were randomly assigned to undergo either a long segment (20 cm; ∼ 50% of ileum) IT or sham surgery. Glucose control was determined by an oral glucose tolerance test (OGTT) on day −7, 0, 14 and 20. Analysis of the incretin hormones glucagon-like peptide 1 (GLP-1), peptide YY (PYY) and insulin was included in the first and third OGTT.ResultsIleal transposition animals showed an early improvement of glucose control after 14 days (area under the curve: IT vs. baseline 314.7 ±229.0 mmol/l × min vs. 564.6 ±268.5 mmol/l × min; p < 0.05). Compared to sham animals, glucose-stimulated GLP-1 and PYY levels were raised (5.75 ±3.73 pmol/l vs. 18.52 ±14.22 pmol/l, p < 0.05; 129.7 ±64.62 pmol/l vs. 164.0 ±62.26 pmol/l, p < 0.05). Body weight gain from postoperative day 5 was greater for sham animals (50.22 ±20.93 γ vs. 16.4 ±25.93 g; p < 0.01).ConclusionsLong segment IT shows a rapid rise in GLP-1 and PYY levels, thus leading to early amelioration of glucose control.

Targeting the gastrointestinal tract to treat type 2 diabetes

“…Lastly, another experimental metabolic surgery still in early human trials is ileal interposition (with or without VSG), which involves resection of 10-20 cm of the distal ileum and its transposition into the proximal jejunum. This procedure results in weight loss, reduced food intake and improved glycaemic regulation in both rodents and humans (Wang et al 2008b, Gagner 2011, Zhang et al 2011, Grueneberger et al 2013, Grueneberger et al 2014, Ramzy et al 2014.…”

Ileal transposition in rats influenced glucose metabolism and HSP70 levels

“…This paper is the third part of a wider experiment which concerned ileal transposition treatment of obesity and insulin resistance, in the obese rat model: Crl:ZUC-Lepr fa Zucker rat [3,13]. All surgical and experimental procedures were precisely described earlier by our research group [3,13], thus in this paper we briefly present only the main points.…”

“…All surgical and experimental procedures were precisely described earlier by our research group [3,13], thus in this paper we briefly present only the main points. The animal experimental protocols were approved by the Ethics Committee of the University of Freiburg [3,9,13]. In short, 11 to 12-week-old, 200-220 g, obese male Zucker rats (Crl:ZUC-Lepr fa ) were purchased from Charles River Breeding Laboratories (Wilmington, Mass).…”

“…After a 7-8 day acclimation period, 10 rats underwent an ileal transposition surgery on 50% of distal ileum [3]. The animals were fasted for 12 hours before surgery.…”

“…This paper is a continuation of a research project examining the long term effect of ileal transposition in term of physiologic background and long-term adaption in Crl:ZUC-Lepr fa Zucker rats [3,13]. The principal goal of this study was to investigate the impact of transposition of 50% of distal ileum on separated, selected parameters of glucose administration and HSP70 concentration levels during in vivo experiments on the Crl:ZUC-Lepr fa rat's liver six months after IT surgery.…”