Wu Dongjiao, Weng Siying, Xu Shuyi, Li Yan, Zhou Jianyang
Department of Rheumatology, Ningbo Municipal Hospital of TCM, Affliated Hospital of Zhejiang Chinese Medical University, Ningbo, China.
Department of Endocrinology, Ningbo Municipal Hospital of TCM, Affliated Hospital of Zhejiang Chinese Medical University, Ningbo, China.
Front Pharmacol. 2023 Mar 14;14:1136778. doi: 10.3389/fphar.2023.1136778. eCollection 2023.
Yiqi Huazhuo Decoction (YD) reduces blood glucose, glycated hemoglobin, body weight, and insulin resistance in patients with type 2 diabetes mellitus (T2DM), but its exact mechanisms are unknown. This study investigated the therapeutic effects and mechanisms of YD on impaired insulin secretion in T2DM rats. T2DM rats were randomized to the model, YD-lo (15 mg/kg/d YD, 10 weeks), YD-hi (30 mg/kg/d YD, 10 weeks), positive drug (TAK-875), and healthy control groups. The rats underwent an oral glucose tolerance test (OGTT), glucose-stimulated insulin secretion (GSIS) test, and serum lipid measurements. High-fat and high-glucose-injured RIN-m5f cells were treated with YD (30 or 150 mg/mL) for 48 h. GPR40 and IP3R-1 expression levels were determined by immunofluorescence, qRT-PCR, and western blot. Compared with the model group, the OGTT area under the curve (AUC) in the YD-hi group was decreased by 26.7%, the insulin release test (IRT) AUC in the YD-hi group was increased by 45.9%, and the GSIS AUC was increased by 33.9% ( < 0.05). Compared with the model cells, the insulin secretion after glucose stimulation in the YD-hi group was increased by 24.5%, similar to the TAK-875 group (23.1%) ( > 0.05). GPR40 and IP3R-1 mRNA in the model cells were decreased by 49.5% and 51.2% compared with the control cells ( < 0.05). In the YD-hi group, GPR40 and IP3R-1 mRNA levels were increased by 58.1% and 39.3% ( < 0.05), similar to the TAK-875 group. The changes in protein expression were similar to mRNA. YD promotes insulin secretion from pancreatic islet β-cell in T2DM rats by regulating the GPR40-IP3R-1 pathway, thereby reducing blood glucose.
益气化浊方（YD）可降低2型糖尿病（T2DM）患者的血糖、糖化血红蛋白、体重和胰岛素抵抗，但其确切机制尚不清楚。本研究探讨了YD对T2DM大鼠胰岛素分泌受损的治疗作用及机制。将T2DM大鼠随机分为模型组、YD低剂量组（15mg/kg/d YD，共10周）、YD高剂量组（30mg/kg/d YD，共10周）、阳性药物组（TAK - 875）和健康对照组。大鼠进行口服葡萄糖耐量试验（OGTT）、葡萄糖刺激胰岛素分泌（GSIS）试验及血脂测定。用YD（30或150mg/mL）处理高脂高糖损伤的RIN - m5f细胞48小时。通过免疫荧光、qRT - PCR和蛋白质印迹法测定GPR40和IP3R - 1的表达水平。与模型组相比，YD高剂量组的OGTT曲线下面积（AUC）降低了26.7%，胰岛素释放试验（IRT）AUC增加了45.9%，GSIS AUC增加了33.9%（P<0.05）。与模型细胞相比，YD高剂量组葡萄糖刺激后的胰岛素分泌增加了24.5%，与TAK - 875组（23.1%）相似（P>0.05）。与对照细胞相比，模型细胞中的GPR40和IP3R - 1 mRNA分别降低了49.5%和51.2%（P<0.05）。在YD高剂量组中，GPR40和IP3R - 1 mRNA水平分别增加了58.1%和39.3%（P<0.05），与TAK - 875组相似。蛋白质表达的变化与mRNA相似。YD通过调节GPR40 - IP3R - 1通路促进T2DM大鼠胰岛β细胞分泌胰岛素，从而降低血糖。
