Ileal interposition surgery-induced improvement of hyperglycemia and insulin resistance in Goto-Kakizaki rats by upregulation of TCF7L2 expression

Abstract

The aim of this study was to investigate the effects of ileal interposition (IT) on glucose and insulin resistance (IR) in type 2 diabetic mellitus (T2DM), and the role of T-cell factor 7-like 2 (TCF7L2), formerly known as TCF4, in the downregulation of hyperglycemia following IT. Goto-Kakizaki (GK) rats subjected to IT surgery (GK-IT group), GK rats subjected to sham surgery (GK-Sham group) and Wistar (WS) rats subjected to sham surgery (WS-Sham group) were investigated in this study. Fasting plasma glucose, body weight, food intake per 1 kg body weight, insulin and a homeostasis model assessment of insulin resistance (HOMA-IR) were measured pre- and post-surgery. The rats were euthanized 28 days post-surgery and the pancreas of each rat was dissected. The expression levels of TCF7L2 mRNA and protein were analyzed by quantitative RT-PCR and western blotting, respectively. Our results revealed that IT improved both fasting plasma glucose levels and IR in GK rats by upregulating the expression of the TCF7L2 protein. IT provides a valuable therapeutic option for patients with T2DM. Upregulation of TCF7L2 protein expression may be a possible mechanism underlying the improvement of T2DM following IT.

Contribution of the distal small intestine to metabolic improvement after bariatric/metabolic surgery: Lessons from ileal transposition surgery

“…Increased GLP‐1 might explain the improved β‐cell function after IT surgery. Intriguingly, in GK rats, IT surgery increased GLP‐1 receptor and TCF7L2 expression in the pancreas, and decreased β‐cell apoptosis, which could be additional mechanisms of improved β‐cell function after IT surgery.…”

Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21

“…Among these procedures, ileal transposition (IT) is a novel surgical technique that involves translocation of a segment of the ileum proximally into the upper jejunum without altering the length of the gastrointestinal tract or gastric restriction (Pok and Lee, 2014 ). IT surgery has been reported to induce weight loss, improve glucose and lipid metabolism and increase insulin sensitivity in diabetic or obese rats (Culnan et al, 2010 ; Cummings et al, 2010 ; Ikezawa et al, 2012 ; Sun et al, 2013 , 2014 ; Ramzy et al, 2014 ; Oh et al, 2016 ). Further, the feasibility, safety, and efficacy of the combination of IT surgery and sleeve gastrectomy in diabetic patients have been evaluated in several studies (De Paula et al, 2010 ; DePaula et al, 2012 ; Celik et al, 2015 ).…”

“…Goto-Kakizaki (GK) rats, a non-obese Wistar substrain rat with spontaneous diabetes, have been reported to exhibit characteristics that are functionally present in human T2DM patients (Goto et al, 1975 ; Akash et al, 2013 ). GK rats have been widely used in research relating to IT surgery (Yan et al, 2012 ; Sun et al, 2013 ). Therefore, in the present study, experiments were conducted on GK rats to investigate the effects of IT surgery on glucose and lipid metabolism and the possible relationship of IT surgery with the FGF21 signaling pathway.…”

Structural and Functional Transformation of the Small Intestine Wall in the Conditions of the Functioning of the Artificial Urinary Reservoir in the Experiment

“…The study of morphological changes in the wall of the artificial bladder continues from the moment of the first conduit from the region of the ileum. Many researchers note the progressive atrophy of the villi and microvilli [10], and the number of glass-shaped cells decreases with time [11,18].…”