Improvements of Glucose and Lipid Metabolism After Jejuno-ileal Circuit Procedure in a Non-obese Diabetic Rat Model.

Abstract

In a recent study, we showed a jejuno-ileal circuit (JIC) procedure that effectively improved glucose homeostasis, but the intrinsic mechanism requires further studies. Furthermore, the role of JIC in lipid metabolism is also unknown. Given that adiposity aggravates insulin sensitivity, we hypothesize that the JIC procedure improves fat metabolism and thus further contributes to diabetic remission. The aim of this study was to investigate the effects of JIC surgery on lipid metabolism and glucose homeostasis in a non-obese diabetic rat model. Fourteen high-fat diet and low-dose streptozotocin-induced diabetic rats were randomly divided into JIC and sham-JIC groups. Body weight, food intake, glucose tolerance, insulin resistance, serum lipid parameters, glucagon-like peptide 1 (GLP-1), and adipose-derived hormones were measured. At 12weeks postoperatively, the expressions of hepatic fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were measured by Western blot. The lipid content of liver was assessed by hematoxylin-eosin staining and Oil Red O staining. The enteroendocrine cells in the distal ileum were examined by immunohistochemical staining. Relative to the sham group, the JIC rats exhibited significant improvements in glucose tolerance, insulin resistance, and dyslipidemia without weight loss, showing increased GLP-1 and adiponectin and decreased leptin. JIC also reduced the expression of FAS and ACC in the liver, exhibited improved hepatic fat content, and raised the levels of GLP-1 and chromogranin A in the distal gut. JIC alleviated lipometabolic disorders in hyperglycemic rats, which may contribute to the amelioration of insulin sensitivity and glycemic control.