Luo Meng-Juan, Wang Ying, Chen Si-Yu, Yang Ze-Min
Department of Biochemistry and Molecular Biology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University/Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangzhou, China.
Front Pharmacol. 2022 Aug 17;13:916603. doi: 10.3389/fphar.2022.916603. eCollection 2022.
Sweet taste receptors (STRs) play an important role in glucose metabolism, and type 2 diabetic rats have abnormal expressions of STRs in multiple tissues. polysaccharides (APS) has shown a significant therapeutic effect on type 2 diabetes mellitus (T2DM), but its mechanism needs to be further clarified. T2DM rat model was induced by intraperitoneal streptozotocin injection and treated with APS for 8 weeks. Daily indicators of experimental rats were observed, and expression levels of STRs and genes related to glycolipid metabolism were determined by real-time quantitative PCR and western blot. The present study revealed that APS alleviated the symptoms of T2DM rats, improved HOMA-IR and promoted insulin secretion. Gene expression analysis found that APS significantly increased the expressions of signaling molecules in STRs pathways, including taste receptor family 1 member 2 (T1R2), α-gustducin (Gα) and transient receptor potential cation channel subfamily member 5 (TRPM5), and reversed the expressions of genes related to glucolipid metabolism, including glucose transporters 2 and 4 (GLUT2 and GLUT4), pyruvate carboxylase (PC), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) in the liver of T2DM rats. However, APS had no influences on the expressions of genes, including glycogen synthase kinase-3 beta (GSK-3β), pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of T2DM rats. These results suggested that the physiological roles of STRs in the liver were involved with glucose transport and metabolism. APS alleviated T2DM rats by activating the STRs pathway, and promoted glucose transport and lipogenesis.
甜味受体（STRs）在葡萄糖代谢中起重要作用，2型糖尿病大鼠多种组织中STRs表达异常。黄芪多糖（APS）对2型糖尿病（T2DM）已显示出显著治疗作用，但其机制尚需进一步阐明。通过腹腔注射链脲佐菌素诱导建立T2DM大鼠模型，并用APS治疗8周。观察实验大鼠的日常指标，采用实时定量PCR和蛋白质印迹法检测STRs及糖脂代谢相关基因的表达水平。本研究表明，APS可缓解T2DM大鼠症状，改善胰岛素抵抗指数（HOMA-IR）并促进胰岛素分泌。基因表达分析发现，APS可显著增加STRs通路中信号分子的表达，包括味觉受体家族1成员2（T1R2）、α-味导素（Gα）和瞬时受体电位阳离子通道亚家族成员5（TRPM5），并逆转T2DM大鼠肝脏中糖脂代谢相关基因的表达，包括葡萄糖转运蛋白2和4（GLUT2和GLUT4）、丙酮酸羧化酶（PC）、脂肪酸合酶（FAS）和乙酰辅酶A羧化酶（ACC）。然而，APS对T2DM大鼠肝脏中糖原合酶激酶-3β（GSK-3β）、丙酮酸激酶（PK）和磷酸烯醇式丙酮酸羧激酶（PEPCK）等基因的表达无影响。这些结果提示，STRs在肝脏中的生理作用与葡萄糖转运和代谢有关。APS通过激活STRs通路减轻T2DM大鼠症状，促进葡萄糖转运和脂肪生成。
