• Yiying Liu, Yue Zeng, Ying Miao, Xiaoling Cheng, Sijie Deng, Xinlin Hao, Yuefei Jiang, and Qin Wan.
• Department of Endocrinology, The Affiliated Hospital of Southwest Medical University , Luzhou, Sichuan, China.
• Postgrad Med. 2020 Nov 1; 132 (8): 720-726.

ObjectivesThis study aimed to investigate the relationships among islet function, the Nrf2 pathway, and insulin receptor substrate 2 (IRS2) in type 2 diabetes mellitus (T2DM), prediabetes mellitus (IGR), and normal glucose tolerance (NGT) populations.MethodsThree hundred cases each were selected for the NGT, IGR, and T2DM groups; FBG, 2hPG, HbA1 c, FINS, TG, TC, HDL-C, and LDL-C levels and serum levels of nuclear factor in E2-related factor 2 (Nrf2), insulin receptor substrate 2 (IRS2), tumor necrosis factor alpha (TNF-α), and heme oxygenase 1 (HO-1) were evaluated.ResultsThe T2DM group had lower islet β-cell function index and insulin sensitivity index than the NGT and IGR groups (P < 0.05). The Nrf2, IRS2, and HO-1 levels in the NGT, IGR, and T2DM groups followed a decreasing trend in the order mentioned, whereas the TNF-α levels followed an increasing trend.ConclusionsUpon impairment of glucose regulation, the expression of TNF-α in the human body increased, which indicated the aggravation of oxidative stress (OS) and the inflammatory response. Islet function was maintained in the pre-diabetic population, and concurrently, the TNF-α, Nrf2, and HO-1 levels were moderately elevated, the expression of IRS2 was marginally inhibited, and the Nrf2 pathway was activated under mild OS stimulus to resist OS, inflammation, and injury, which may have been mediated through PI3 K/AKT. In patients with T2DM, islet function was significantly poorer, TNF-α amplification was enhanced significantly, and Nrf2, HO-1, and IRS2 expression reduced significantly; this suggested that, along with the aggravation of OS and the inflammatory response, Nrf2 pathway activation and HO-1 expression were both inhibited, the antioxidant capacity of the body was reduced, IRS2 degradation increased, and islet function was impaired.

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