Влияние Roux-en-Y гастрошунтирования и продольной резекции желудка на метаболические и гормональные показатели и гипоталамический сигналинг у крыс с диабетом 2 типа

Abstract

Bariatric surgery is widely used to correct the metabolic dysfunctions in type 2 diabetes mellitus (T2DM), but the mechanisms of its action are not fully understood. The aim of the work was to study the effect of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on the metabolic and hormonal parameters and on the expression of the hypothalamic genes encoding appetite-regulating factors and the components of signaling systems controlling an energy metabolism in male rats with T2DM without obesity. The T2DM was induced by a 20-week high-fat diet and treatment of rats with 20 mg/kg of streptozotocin (STZ) at the 12th week of the experiment. The operations were performed 3 weeks after STZ treatment. The glucose sensitivity and the hormonal parameters were evaluated at the 19th week, and the hypothalamic tissues were taken at the 20th week to evaluate the gene expression. In rats with T2DM, both operations reduced the food intake, decreased the postprandial glucose levels, normalized the leptin levels, and lowered the plasma ghrelin levels in T2DM. The SG, which, in comparison with RYGB, had a lesser effect on the glucose homeostasis and the ghrelin level, reduced the food intake more effectively and, unlike RYGB, restored the glucagon-like peptide-1 (GLP-1) level decreased in T2DM. The RYGB led to a decrease in the expression of orexigenic genes, encoding agouti-like peptide and ghrelin receptor, increased in T2DM, and to an increase in the expression of anorexigenic genes, encoding the MC3- and MC4-melanocortin, the 5-HT2C-serotonin and leptin receptors and pro-opiomelanocortin. The largest contribution to the effects of SG is made by a significant increase in the hypothalamic expression of the GLP-1 receptor gene, associated with an increase in the plasma GLP-1 level. Thus, the RYGB and SG can be effective to correct the metabolic and functional dysfunctions in non-obese T2DM, and the restoration of the balance between the hypothalamic orexigenic and anorexigenic pathways makes a significant contribution to these effects.