Department of Food Science and Biotechnology, College of Agriculture, Life, & Environmental Sciences, Chungbuk National University, Cheongju, Korea.
J Food Biochem. 2021 Dec;45(12):e13993. doi: 10.1111/jfbc.13993. Epub 2021 Nov 3.
Type 2 diabetes is characterized by insulin resistance (IR) and increased hepatic glucose production. MicroRNAs (miRs) are considered regulators of glucose metabolism. This study evaluated anti-diabetic activity of hydroxybenzoic acid derivatives and determined the involvement of miR-1271. Among the hydroxybenzoic acid derivatives, gallic acid (GA) showed the best anti-diabetic activity. GA improved free fatty acid (FFA)-induced hepatic IR, increased glucose consumption, and decreased reactive oxygen species. GA inhibited the upregulation of miR-1271 induced by FFA and upregulated its targets such as p-IRS, p-PI3K, p-AKT, and p-FOXO1, accompanied by the regulation of glucose metabolism genes. The involvement of miR-1271 in the protective effect of GA against IR was further confirmed in the presence of miR-1271 mimic or miR-1271 inhibitor. Our results suggest that GA attenuates IR via the miR-1271/IRS/PI3K/AKT/FOXO1 pathway and thus might be considered for the management of IR. PRACTICAL APPLICATIONS: MicroRNAs can regulate insulin resistance by affecting protein expressions involved in insulin signaling. Experimental data suggest that some phytochemicals regulate the expression of various microRNAs. However, it is not clear whether phenolic acids play any role in the hepatic insulin signaling pathway through the regulation of microRNA expression. This study assessed the anti-diabetic activity of hydroxybenzoic acid derivatives through down-regulation of microRNA-1271 and its association with the IRS1/PI3K/AKT/FOXO1 pathways. This research will be able to offer basic information regarding a potential therapeutic strategy to control hepatic insulin resistance.
2 型糖尿病的特征是胰岛素抵抗 (IR) 和肝葡萄糖生成增加。MicroRNAs (miRs) 被认为是葡萄糖代谢的调节剂。本研究评估了羟基苯甲酸衍生物的抗糖尿病活性，并确定了 miR-1271 的参与。在羟基苯甲酸衍生物中，没食子酸 (GA) 表现出最好的抗糖尿病活性。GA 改善游离脂肪酸 (FFA) 诱导的肝 IR，增加葡萄糖消耗，减少活性氧。GA 抑制 FFA 诱导的 miR-1271 上调，并上调其靶标，如 p-IRS、p-PI3K、p-AKT 和 p-FOXO1，并伴有葡萄糖代谢基因的调节。在存在 miR-1271 模拟物或 miR-1271 抑制剂的情况下，进一步证实了 miR-1271 在 GA 对 IR 的保护作用中的参与。我们的研究结果表明，GA 通过 miR-1271/IRS/PI3K/AKT/FOXO1 途径减轻 IR，因此可能被考虑用于管理 IR。实际应用：MicroRNAs 可以通过影响胰岛素信号通路中涉及的蛋白质表达来调节胰岛素抵抗。实验数据表明，一些植物化学物质通过调节各种 microRNAs 的表达来调节。然而，目前尚不清楚酚酸是否通过调节 microRNA 表达在肝胰岛素信号通路中发挥作用。本研究通过下调 microRNA-1271 及其与 IRS1/PI3K/AKT/FOXO1 途径的关联，评估了羟基苯甲酸衍生物的抗糖尿病活性。这项研究将能够提供有关控制肝胰岛素抵抗的潜在治疗策略的基本信息。
