Autor: |
Kornyushin OV; V.A.Almazov National Medical Research Centre, 2 Akkuratova str., St. Petersburg 197341, Russian Federation., Bakhtyukov AA; I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, 44 pr. Toreza, St. Petersburg 194223, Russian Federation; e-mail: alex_shpakov@list.ru., Zorina II; I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, 44 pr. Toreza, St. Petersburg 194223, Russian Federation; e-mail: alex_shpakov@list.ru., Toropova YG; V.A.Almazov National Medical Research Centre, 2 Akkuratova str., St. Petersburg 197341, Russian Federation., Derkach KV; I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, 44 pr. Toreza, St. Petersburg 194223, Russian Federation; e-mail: alex_shpakov@list.ru., Berko OM; I.P.Pavlov First Saint Petersburg State Medical University, 6-8 L'va Tolstogo str., St. Petersburg 197022, Russian Federation., Todosenko MN; Immanuel Kant Baltic Federal University, 14 Alexandra Nevskogo str., Kaliningrad 236016, Russian Federation., Litvinova LS; Immanuel Kant Baltic Federal University, 14 Alexandra Nevskogo str., Kaliningrad 236016, Russian Federation., Shpakov AO; I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, 44 pr. Toreza, St. Petersburg 194223, Russian Federation; e-mail: alex_shpakov@list.ru., Galagudza MM; V.A.Almazov National Medical Research Centre, 2 Akkuratova str., St. Petersburg 197341, Russian Federation. |
Abstrakt: |
Currently, one of the approaches to correct metabolic disorders in the type 2 diabetes mellitus (DM2) with obesity are bariatric surgery (BS), including sleeve gastrectomy (SG), gastric bypass (GB) and ileal transposition (IT). However, their effectiveness and impact on the hypothalamic signaling and hormonal status in severe forms of DM2 without obesity remain little studied. The aim of the work was to study the effect of IT, SG and GB on the insulin, leptin, ghrelin and glucagon-like peptide-1 (GLP-1) levels in the blood and on the expression of the genes encoding the main components of the hypothalamic signaling systems in rats with decompensated form of DM2, which was induced by a high-fat diet (3 months) and a single low dose of streptozotocin (25 mg/kg, 2 months after the start of the diet). In diabetic rats, a significantly expressed hyperglycemia, an impaired glucose tolerance, a decrease in glucose-stimulated GLP-1 level, a slight decrease in the insulin and leptin levels and an slight increase in ghrelin level were detected. In the hypothalamus, the expression of the genes encoding GLP-1 receptor, orexigenic agouti-related peptide (AgRP), as well as phosphotyrosine phosphatase 1B and SOCS3, the negative regulators of the leptin and insulin pathways was increased. In diabetic rats, the IT reduced the glucose levels 120 minutes after glucose load, increased the basal and glucose-stimulated GLP-1 levels, normalized the gene expression for phosphotyrosine phosphatase 1B, SOCS3, AgRP and GLP-1 receptor, which indicates the restoration of the hypothalamic signaling responsible for the control of energy metabolism and insulin sensitivity. In the case of SG and GB, an improvement in the glucose tolerance was found, and in the case of SG, an increase in the basal and glucose-stimulated GLP-1 levels was shown. However, no significant effect on the expression of the hypothalamic genes in SG and GB was found. Thus, IT is the most effective of all studied BS in the treatment of severe forms of DM2 without obesity. |