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[不同类型的减肥手术对失代偿型2型糖尿病大鼠代谢和激素参数的影响。]

[The effect of different types of bariatric surgery on the metabolic and hormonal parameters in rats with decompensed form of type 2 diabetes mellitus.].

作者信息

Kornyushin O V, Bakhtyukov A A, Zorina I I, Toropova Y G, Derkach K V, Berko O M, Todosenko M N, Litvinova L S, Shpakov A O, Galagudza M M

机构信息

V.A.Almazov National Medical Research Centre, 2 Akkuratova str., St. Petersburg 197341, Russian Federation.

I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, 44 pr. Toreza, St. Petersburg 194223, Russian Federation; e-mail:

出版信息

Adv Gerontol. 2019;32(1-2):85-92.

Abstract

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.

摘要

目前,针对伴有肥胖症的2型糖尿病(DM2)纠正代谢紊乱的方法之一是减重手术(BS),包括袖状胃切除术(SG)、胃旁路术(GB)和回肠转位术(IT)。然而,对于无肥胖症的严重DM2形式,它们的有效性以及对下丘脑信号传导和激素状态的影响仍鲜少被研究。这项工作的目的是研究IT、SG和GB对由高脂饮食(3个月)和单次低剂量链脲佐菌素(25 mg/kg,在饮食开始2个月后)诱导的失代偿型DM2大鼠血液中胰岛素、瘦素、胃饥饿素和胰高血糖素样肽-1(GLP-1)水平以及对编码下丘脑信号系统主要成分的基因表达的影响。在糖尿病大鼠中,检测到显著的高血糖、葡萄糖耐量受损、葡萄糖刺激的GLP-1水平降低、胰岛素和瘦素水平略有下降以及胃饥饿素水平略有升高。在下丘脑中,编码GLP-1受体、促食欲的刺鼠相关肽(AgRP)以及瘦素和胰岛素途径的负调节因子磷酸酪氨酸磷酸酶1B和SOCS3的基因表达增加。在糖尿病大鼠中,IT降低了葡萄糖负荷后120分钟的血糖水平,增加了基础和葡萄糖刺激的GLP-1水平,使磷酸酪氨酸磷酸酶1B、SOCS3、AgRP和GLP-1受体的基因表达正常化,这表明负责能量代谢和胰岛素敏感性控制的下丘脑信号传导得以恢复。在SG和GB的情况下,发现葡萄糖耐量有所改善,在SG的情况下,基础和葡萄糖刺激的GLP-1水平有所升高。然而,未发现SG和GB对下丘脑基因表达有显著影响。因此,在治疗无肥胖症的严重DM2形式方面,IT是所有研究的减重手术中最有效的。

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