Stanciu Silviu Marcel, Jinga Mariana, Miricescu Daniela, Stefani Constantin, Nica Remus Iulian, Stanescu-Spinu Iulia-Ioana, Vacaroiu Ileana Adela, Greabu Maria, Nica Silvia
Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital, "Dr. Carol Davila", 010825 Bucharest, Romania.
Discipline of Biochemistry, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania.
Biomedicines. 2024 Aug 8;12(8):1802. doi: 10.3390/biomedicines12081802.
Worldwide, diabetes mellitus (DM) and cardiovascular diseases (CVDs) represent serious health problems associated with unhealthy diet and sedentarism. Metabolic syndrome (MetS) is characterized by obesity, dyslipidemia, hyperglycemia, insulin resistance (IR) and hypertension. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase with key roles in glucose and lipid metabolism, cell growth, survival and proliferation. mTOR hyperactivation disturbs glucose metabolism, leading to hyperglycemia and further to IR, with a higher incidence in the Western population. Metformin is one of the most used hypoglycemic drugs, with anti-inflammatory, antioxidant and antitumoral properties, having also the capacity to inhibit mTOR. mTOR inhibitors such as rapamycin and its analogs everolimus and temsirolimus block mTOR activity, decrease the levels of glucose and triglycerides, and reduce body weight. The link between mTOR dysregulation, IR, hypertension and mTOR inhibitors has not been fully described. Therefore, the main aim of this narrative review is to present the mechanism by which nutrients, proinflammatory cytokines, increased salt intake and renin-angiotensin-aldosterone system (RAAS) dysregulation induce mTOR overactivation, associated further with IR and hypertension development, and also mTOR inhibitors with higher potential to block the activity of this protein kinase.
在全球范围内，糖尿病（DM）和心血管疾病（CVD）是与不健康饮食和久坐不动相关的严重健康问题。代谢综合征（MetS）的特征是肥胖、血脂异常、高血糖、胰岛素抵抗（IR）和高血压。雷帕霉素的哺乳动物靶点（mTOR）是一种丝氨酸/苏氨酸激酶，在葡萄糖和脂质代谢、细胞生长、存活和增殖中起关键作用。mTOR过度激活会扰乱葡萄糖代谢，导致高血糖并进一步发展为IR，在西方人群中发病率更高。二甲双胍是最常用的降糖药物之一，具有抗炎、抗氧化和抗肿瘤特性，也有抑制mTOR的能力。mTOR抑制剂如雷帕霉素及其类似物依维莫司和替西罗莫司可阻断mTOR活性，降低血糖和甘油三酯水平，并减轻体重。mTOR失调、IR、高血压与mTOR抑制剂之间的联系尚未完全阐明。因此，本叙述性综述的主要目的是阐述营养素、促炎细胞因子、盐摄入增加和肾素-血管紧张素-醛固酮系统（RAAS）失调诱导mTOR过度激活的机制，这进一步与IR和高血压的发展相关，同时还介绍具有更高潜力阻断这种蛋白激酶活性的mTOR抑制剂。
