Skuratovskaia Daria, Vulf Maria, Chasovskikh Nataliya, Komar Aleksandra, Kirienkova Elena, Shunkin Egor, Zatolokin Pavel, Litvinova Larisa
Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, Kaliningrad, Russia.
Department of Medical and Biological Cybernetics, Siberian State Medical University, Tomsk, Russia.
Front Genet. 2021 Apr 20;12:612501. doi: 10.3389/fgene.2021.612501. eCollection 2021.
Type 2 diabetes mellitus (T2DM) is one of the most prominent and socially significant problems. The present study aimed to identify the mechanisms of interaction of critical regulators of carbohydrate metabolism using bioinformatics and experimental methods and to assess their influence on the development of T2DM. We conducted an search for the relationship of hormones and adipokines and performed functional annotation of the receptors for ghrelin and incretins. Hormones and adipokines were assessed in the plasma of obese patients with and without T2DM as well as after laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) surgeries. Incretin- and ghrelin-associated functions and metabolic processes were discovered. Low ghrelin levels were observed in obese patients without T2DM compared with healthy volunteers and the other groups. The highest ghrelin levels were observed in obese patients with T2DM. This defense mechanism against insulin resistance could be realized through the receptors G-protein-coupled receptor (GPCR), growth hormone secretagogue receptor (GHSR), and growth hormone-releasing hormone receptor (GHRHR). These receptors are associated with proliferative, inflammatory, and neurohumoral signaling pathways and regulate responses to nutrient intake. Signaling through the GPCR class unites ghrelin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide (GLP)-1. Ghrelin impairs carbohydrate and lipid metabolism in obese patients. Ghrelin is associated with elevated plasma levels of insulin, glucagon, and leptin. Specific activation of receptors and modulation by posttranslational modifications of ghrelin can control IR's development in obesity, which is a promising area for research.
2型糖尿病（T2DM）是最突出且具有重大社会意义的问题之一。本研究旨在利用生物信息学和实验方法确定碳水化合物代谢关键调节因子的相互作用机制，并评估它们对T2DM发生发展的影响。我们搜索了激素和脂肪因子之间的关系，并对胃饥饿素和肠促胰岛素的受体进行了功能注释。在患有和未患T2DM的肥胖患者血浆中，以及在腹腔镜袖状胃切除术（LSG）和Roux-en-Y胃旁路术（RYGB）后评估了激素和脂肪因子。发现了与肠促胰岛素和胃饥饿素相关的功能及代谢过程。与健康志愿者及其他组相比，未患T2DM的肥胖患者胃饥饿素水平较低。患T2DM的肥胖患者胃饥饿素水平最高。这种针对胰岛素抵抗的防御机制可能通过G蛋白偶联受体（GPCR）、生长激素促分泌素受体（GHSR）和生长激素释放激素受体（GHRHR）实现。这些受体与增殖、炎症和神经体液信号通路相关，并调节对营养摄入的反应。通过GPCR类的信号传导将胃饥饿素、胰高血糖素、葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽（GLP）-1联系起来。胃饥饿素会损害肥胖患者的碳水化合物和脂质代谢。胃饥饿素与血浆中胰岛素、胰高血糖素和瘦素水平升高有关。受体的特异性激活以及胃饥饿素的翻译后修饰调节可以控制肥胖中胰岛素抵抗的发展，这是一个很有前景的研究领域。
