Sleeve Gastrectomy With Modified Jejunoileal Bypass Model in Goto-Kakizaki Rats

Abstract

The objective of this study was to develop a nonobese diabetic rat model for sleeve gastrectomy with modified jejunoileal bypass (SG/MJIB) and to investigate its effectiveness and safety for inducing diabetic control. Thirty-five 13-week-old male Goto-Kakizaki rats were randomly assigned to the pair-fed to sham-operated SG/MJIB (PFSO-SG/MJIB), SG/MJIB, PFSO-SG, SG, and control groups. The experimental period was 16 weeks postoperatively. Body weight; food intake; glycemic control outcomes; and ghrelin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide, and insulin levels were measured. The operated and PFSO groups showed significant weight loss 4 weeks postoperatively compared with the controls. The SG/MJIB and SG groups exhibited a significant improvement in oral glucose tolerance and insulin tolerance compared with the PFSO and control groups. The improved effects in the SG/MJIB group were better than those in the SG group. The SG/MJIB and SG groups showed decreased fasting ghrelin levels and increased levels of GLP-1 secretion 2 and 16 weeks postoperatively. Compared with the SG group, only the SG/MJIB group showed higher glucose-stimulated GLP-1 levels and significantly improved insulin secretion. SG/MJIB may be an effective, steady hypoglycemic surgical model, showing better diabetic control than SG. The hindgut may play a direct role in ameliorating glucose homeostasis. More than 90% of patients with diabetes have type 2 diabetes mellitus (T2DM). Even with strict hyperglycemia control, evidence for reducing complications related to T2DM has been reported 2 ; nevertheless, current therapies, such as diet, exercise, behavior modification, oral hypoglycemic agents, and insulin, can rarely help patients return 3 Recent data proved that the most reliable treatment for the long-term management of T2DM is surgical intervention.4-6 Surgical techniques for T2DM treatment are based on intake restriction, malabsorption, or both of these. However, none of the currently performed operations can provide unanimous treatment effects or a clear therapeutic mechanism. 7,8 Among the operations performed, adjustable gastric banding achieves hypoglycemia mainly through a limited food intake. Although this surgical method is relatively safe, the glycemic regulatory effect is far from satisfactory; complications, such as intragastric erosion or band slippage, may occur 9 ; and the reoperation rate may be .10%.10 Jejunoileal bypass (JIB) has been the most effective T2DM treatment 11 ; however, because of its severe complications, JIB has been abandoned by most surgeons. 12 Other procedures that combine gastritis and malabsorption, such as Roux-en-Y bypass, exclude most parts of the stomach, making this organ and the biliary ducts inaccessible to the usual endoscopic examinations, 13,14 which is not very suitable in high-risk patients. 15Recently, sleeve gastrectomy (SG) was reported with a hypoglycemic effect similar to that of Rouxen-Y bypass. 4 However, the use of SG cannot explain the mechanism of T2DM...