Interdisciplinary Department of Medicine, University of Bari, "Aldo Moro", Bari, Italy.
Department of Mental Health, University of Bari Aldo Moro, Local Health Authority Bari, Bari, Italy.
Endocr Metab Immune Disord Drug Targets. 2024;24(3):321-332. doi: 10.2174/1871530323666230803095118.
Chronic stress is a condition of pressure on the brain and whole body, which in the long term may lead to a frank disease status, even including type 2 diabetes (T2D). Stress activates the hypothalamus-pituitary-adrenal axis with release of glucocorticoids (GCs) and catecholamines, as well as activation of the inflammatory pathway of the immune system, which alters glucose and lipid metabolism, ultimately leading to beta-cell destruction, insulin resistance and T2D onset. Alteration of the glucose and lipid metabolism accounts for insulin resistance and T2D outcome. Furthermore, stress-related subversion of the intestinal microbiota leads to an imbalance of the gut-brain-immune axis, as evidenced by the stress-related depression often associated with T2D. A condition of generalized inflammation and subversion of the intestinal microbiota represents another facet of stress-induced disease. In fact, chronic stress acts on the gut-brain axis with multiorgan consequences, as evidenced by the association between depression and T2D. Oxidative stress with the production of reactive oxygen species and cytokine-mediated inflammation represents the main hallmarks of chronic stress. ROS production and pro-inflammatory cytokines represent the main hallmarks of stress-related disorders, and therefore, the use of natural antioxidant and anti-inflammatory substances (nutraceuticals) may offer an alternative therapeutic approach to combat stress-related T2D. Single or combined administration of nutraceuticals would be very beneficial in targeting the neuro-endocrine-immune axis, thus, regulating major pathways involved in T2D onset. However, more clinical trials are needed to establish the effectiveness of nutraceutical treatment, dosage, time of administration and the most favorable combinations of compounds. Therefore, in view of their antioxidant and anti-inflammatory properties, the use of natural products or nutraceuticals for the treatment of stress-related diseases, even including T2D, will be discussed. Several evidences suggest that chronic stress represents one of the main factors responsible for the outcome of T2D.
慢性应激是大脑和全身压力的一种状态，长期可能导致明显的疾病状态，甚至包括 2 型糖尿病（T2D）。应激激活下丘脑-垂体-肾上腺轴，释放糖皮质激素（GCs）和儿茶酚胺，以及激活免疫系统的炎症途径，改变葡萄糖和脂质代谢，最终导致β细胞破坏、胰岛素抵抗和 T2D 发病。葡萄糖和脂质代谢的改变导致胰岛素抵抗和 T2D 结果。此外，与应激相关的肠道微生物群的改变导致肠道-大脑-免疫轴失衡，应激相关的抑郁症常与 T2D 相关就是证据。全身性炎症和肠道微生物群的改变代表了应激诱导疾病的另一个方面。事实上，慢性应激通过多器官对肠道-大脑轴起作用，正如抑郁症与 T2D 之间的关联所证明的那样。氧化应激伴随着活性氧（ROS）的产生和细胞因子介导的炎症代表了慢性应激的主要特征。ROS 产生和促炎细胞因子代表了应激相关疾病的主要特征，因此，使用天然抗氧化和抗炎物质（营养保健品）可能提供一种对抗应激相关 T2D 的替代治疗方法。营养保健品的单一或联合给药将非常有益于靶向神经内分泌免疫轴，从而调节 T2D 发病相关的主要途径。然而，还需要更多的临床试验来确定营养保健品治疗的有效性、剂量、给药时间和最有利的化合物组合。因此，鉴于其抗氧化和抗炎特性，天然产物或营养保健品用于治疗应激相关疾病，甚至包括 T2D，将被讨论。有几项证据表明，慢性应激是导致 T2D 结果的主要因素之一。
