Mechanism and Effect of Gegen Qinlian Decoction in Regulating Insulin Secretion Based on p38-PKD1 Signaling Pathway in Gestational Diabetes Mellitus Rats
Objective To investigate the effects and mechanisms of Gegen Qinlian Decoction(GGQLD)on a mouse model of gestational diabetes mellitus(GDM).Methods A genetic GDM mouse model was established using C57BL//KsJdb/+(db/+)pregnant mice,while C57BUKsJ+/+(wild-type)pregnant mice were used as controls.The model mice were randomly divided into the model group,low-dose GGQLD group,high-dose GGQLD group,and positive drug group(metformin),with 10 mice in each group.The treatment groups received treatment from the day of pregnancy,while the control and model groups were administered an equivalent amount of physiological saline.The study assessed the safety of GGQLD on GDM mice and their offspring,examining glucose tolerance,insulin tolerance,insulin levels in serum and pancreatic tissue,pancreatic histopathological changes through tissue sections,and the transcription levels of insulin generation and secretion-related factors in pancreatic tissue using RT-PCR.Additionally,cell proliferation in Min6 cells,as well as insulin secretion under high-glucose stimulation,were evaluated.Results Compared with the GDM model mice,the pathological morphology of the liver and kidneys in the GGQLD and positive drug groups improved.Compared with model group,GDM mice treated with GGQLD showed significant improvements in glucose tolerance and insulin tolerance(P＜0.05),marked improvement in pancreatic morphology,increased insulin levels in serum and pancreatic tissue,and upregulation of transcription levels of insulin generation and secretion-related factors(P＜0.01,P＜0.05).Further mechanistic studies revealed that GGQLD could downregulate the phosphorylation level of p38 protein and upregulate the phosphorylation level of polycystic kidney disease gene 1(PKD1)protein(P＜0.01,P＜0.05).In the Min6 cell model,GGQLD promoted cell proliferation and insulin secretion under high-glucose stimulation(P＜0.01).Using a pharmacological tool to block PKD1,it was found that inhibiting PKD1 weakened the elevating effect of GGQLD on insulin(P＜0.01).Conclusion GGQLD demonstrates good safety for GDM mice and their offspring,and it promotes insulin secretion by regulating the p38-PKD1 signaling pathway,suggesting a potential therapeutic effect on gestational diabetes mellitus.
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