PMID- 36998612 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230401 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 14 DP - 2023 TI - Yiqi Huazhuo decoction increases insulin secretion in type 2 diabetic rats by regulating the pancreatic GPR40-IP3R-1 signaling pathway. PG - 1136778 LID - 10.3389/fphar.2023.1136778 [doi] LID - 1136778 AB - Objective: 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. Methods: 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. Results: 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% (p < 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%) (p > 0.05). GPR40 and IP3R-1 mRNA in the model cells were decreased by 49.5% and 51.2% compared with the control cells (p < 0.05). In the YD-hi group, GPR40 and IP3R-1 mRNA levels were increased by 58.1% and 39.3% (p < 0.05), similar to the TAK-875 group. The changes in protein expression were similar to mRNA. Conclusion: YD promotes insulin secretion from pancreatic islet beta-cell in T2DM rats by regulating the GPR40-IP3R-1 pathway, thereby reducing blood glucose. CI - Copyright (c) 2023 Wu, Weng, Xu, Li and Zhou. FAU - Wu, Dongjiao AU - Wu D AD - Department of Rheumatology, Ningbo Municipal Hospital of TCM, Affliated Hospital of Zhejiang Chinese Medical University, Ningbo, China. FAU - Weng, Siying AU - Weng S AD - Department of Endocrinology, Ningbo Municipal Hospital of TCM, Affliated Hospital of Zhejiang Chinese Medical University, Ningbo, China. FAU - Xu, Shuyi AU - Xu S AD - College of the Third Clinical Medical, Ningbo Municipal Hospital of TCM, Affliated Hospital of Zhejiang Chinese Medical University, Ningbo, China. FAU - Li, Yan AU - Li Y AD - College of the Third Clinical Medical, Ningbo Municipal Hospital of TCM, Affliated Hospital of Zhejiang Chinese Medical University, Ningbo, China. FAU - Zhou, Jianyang AU - Zhou J AD - Department of Endocrinology, Ningbo Municipal Hospital of TCM, Affliated Hospital of Zhejiang Chinese Medical University, Ningbo, China. LA - eng PT - Journal Article DEP - 20230314 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC10043368 OTO - NOTNLM OT - Yiqi Huazhuo decoction OT - free fatty acid receptor 1 OT - impaired insulin secretion OT - pancreatic islet beta-cell OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/04/01 06:00 MHDA- 2023/04/01 06:01 PMCR- 2023/03/14 CRDT- 2023/03/31 02:08 PHST- 2023/01/03 00:00 [received] PHST- 2023/03/06 00:00 [accepted] PHST- 2023/04/01 06:01 [medline] PHST- 2023/03/31 02:08 [entrez] PHST- 2023/04/01 06:00 [pubmed] PHST- 2023/03/14 00:00 [pmc-release] AID - 1136778 [pii] AID - 10.3389/fphar.2023.1136778 [doi] PST - epublish SO - Front Pharmacol. 2023 Mar 14;14:1136778. doi: 10.3389/fphar.2023.1136778. eCollection 2023.