Duodenal-Jejunal Bypass Surgery Ameliorates Glucose Homeostasis and Reduces Endoplasmic Reticulum Stress in the Liver Tissue in a Diabetic Rat Model.

Abstract

Duodenal-jejunal bypass (DJB) has been shown to be an effective surgical treatment for type 2 diabetes mellitus (T2DM). However, the underlying mechanisms are poorly understood. Recently, accumulating evidences suggest that endoplasmic reticulum (ER) stress plays an important role in the development of insulin resistance in T2DM. The present study was designed to investigate the effect of DJB on glucose homeostasis, the ER stress state in the liver tissue, and the involving signaling independently of weight loss. Thirty adult male T2DM Sprague-Dawley (SD) rats induced by high-fat diet and low dose of streptozotocin (STZ) were randomly divided into DJB and sham groups. Ten age-matched male SD rats were assigned as the control group. The parameters of body weight and calorie intake were measured at indicated time points. The glucose tolerance and insulin resistance were detected to evaluate the glucose homeostasis. Serum insulin was determined by enzyme-linked immunosorbent assay (ELISA). The markers of ER stress, the activity of c-Jun N-terminal kinase (JNK) and serine phosphorylation of insulin receptor substrate 1 (IRS-1) in the liver tissue, were determined by Western blotting. DJB induced significant improvements in glucose homeostasis and insulin sensitivity, but without weight loss. DJB improved the ER stress state indicated by decreased protein kinase RNA (PKR)-like ER protein kinase (PERK) and inositol-requiring enzyme 1 (IRE-1) phosphorylation in the liver tissue. The JNK activity and serine phosphorylation of IRS-1 in the liver tissue were significantly reduced after DJB. DJB ameliorates glucose homeostasis. Meanwhile, our study helps to reveal that the reduced hepatic ER stress and the decreased JNK activity may contribute to the improved glucose homeostasis after DJB.