Laboratory of Cellular and Molecular Pharmacology, Chair and Department of Clinical and Experimental Pharmacology, Medical University, 20-090 Lublin, Poland.
Cells. 2023 Jan 31;12(3):460. doi: 10.3390/cells12030460.
The tryptophan-kynurenine pathway (Trp-KYN) is the major route for tryptophan conversion in the brain and in the periphery. Kynurenines display a wide range of biological actions (which are often contrasting) such as cytotoxic/cytoprotective, oxidant/antioxidant or pro-/anti-inflammatory. The net effect depends on their local concentration, cellular environment, as well as a complex positive and negative feedback loops. The imbalance between beneficial and harmful kynurenines was implicated in the pathogenesis of various neurodegenerative disorders, psychiatric illnesses and metabolic disorders, including diabetes mellitus (DM). Despite available therapies, DM may lead to serious macro- and microvascular complications including cardio- and cerebrovascular disease, peripheral vascular disease, chronic renal disease, diabetic retinopathy, autonomic neuropathy or cognitive impairment. It is well established that low-grade inflammation, which often coincides with DM, can affect the function of KP and, conversely, that kynurenines may modulate the immune response. This review provides a detailed summary of findings concerning the status of the Trp-KYN pathway in DM based on available animal, human and microbiome studies. We highlight the importance of the molecular interplay between the deranged (functionally and qualitatively) conversion of Trp to kynurenines in the development of DM and insulin resistance. The Trp-KYN pathway emerges as a novel target in the search for preventive and therapeutic interventions in DM.
色氨酸-犬尿氨酸途径（Trp-KYN）是大脑和外周组织中色氨酸转化的主要途径。犬尿氨酸具有广泛的生物学作用（通常相互矛盾），如细胞毒性/细胞保护、氧化应激/抗氧化或促炎/抗炎。其净效应取决于其局部浓度、细胞环境以及复杂的正反馈和负反馈环。有益和有害犬尿氨酸之间的失衡与各种神经退行性疾病、精神疾病和代谢疾病（包括糖尿病）的发病机制有关。尽管有可用的治疗方法，但糖尿病可能导致严重的大血管和微血管并发症，包括心血管和脑血管疾病、外周血管疾病、慢性肾脏疾病、糖尿病视网膜病变、自主神经病变或认知障碍。众所周知，与糖尿病同时发生的低度炎症会影响 KP 的功能，相反，犬尿氨酸可能会调节免疫反应。本综述根据现有的动物、人类和微生物组研究，详细总结了色氨酸-犬尿氨酸途径在糖尿病中的研究现状。我们强调了 Trp 向犬尿氨酸的紊乱（功能和质量）转化在糖尿病和胰岛素抵抗发展中的分子相互作用的重要性。色氨酸-犬尿氨酸途径作为糖尿病预防和治疗干预措施的新靶点出现。
