Yingli Wu,1,2,* Tiangang Li,1,2,* Biaohua Chen,1,2,* Yi Sun,1,2 Liyun Song,1,2 Yinying Wang,1,2 Yao Bian,1,2 Yong Qiu,1,2 Zhongshan Yang1,2 

1Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650000, People’s Republic of China; 2Engineering Research Center of Classic Formula Regulate Immunity in Chronic Disease Prevention and Treatment, Kunming, Yunnan, 650000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yong Qiu; Yunnan University of Chinese Medicine, Kunming, 650000, People’s Republic of China, Email chenxiaofeng_82@126.com Zhongshan Yang, Yunnan University of Chinese Medicine, Kunming, 650000, People’s Republic of China, Email yangzhongshan@ynucm.edu.cn

Abstract: Type 2 diabetes mellitus (T2DM) is a complex clinical syndrome characterized by insulin resistance and associated with abnormal amino acid metabolism. Tryptophan is an aromatic dietary amino acid that affects T2DM by regulating glycolipid metabolism and insulin resistance. When tryptophan reaches the intestine, it is converted by gut microbiota and tryptophanase into indole derivatives such as indoleacetic acid, indolepropionic acid, and indolealdehyde. These indole derivatives may enhance insulin sensitivity, stimulate insulin secretion, and exert functions such as lowering blood glucose, regulating hepatic oxidative stress, reducing intestinal inflammation, and improving islet cell morphology by acting on the aryl hydrocarbon receptor (AHR) or Pregnane X receptor (PXR). In summary, this review aims to examine the interactions between tryptophan indole derivatives and T2DM thoroughly, elucidate potential therapeutic approaches, and pinpoint areas for further research.

Keywords: type 2 diabetes mellitus, tryptophan, indole derivatives, aryl hydrocarbon receptor, pregnane X receptor