Jingfan Zhang, Yu Chen, Ling Li, Ruiqi Liu, Ping Li
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引用次数: 0
Abstract
This study investigated the therapeutic effects of N1-Methylnicotinamide (MNAM), a metabolic derivative, on T2DM mice induced by a high-fat diet and streptozotocin (STZ), focusing on its impact on the gut microbiome and immune modulation. MNAM significantly reduced hyperglycemia and enhanced insulin secretion, effects that were dependent on the presence of gut microbiota. It also mitigated STZ-induced weight loss and improved islet cell morphology, reducing islet cell mortality and increasing insulin (INS) levels. Flow cytometry analysis showed a decrease in T helper 17 cells (Th17) and an increase in Treg cells after MNAM treatment, corresponding to the upregulation of Treg markers [interleukin (IL)-10, forkhead box P3 (FOXP3)] and downregulation of Th17 markers [IL17A, RAR-related orphan receptor gamma (RORγt)]. Additionally, MNAM raised anti-inflammatory IL-10 levels while reducing pro-inflammatory cytokines [IL-17α, tumor necrosis factor (TNF-α), IL-6]. Microbiome analysis revealed decreased diversity and increased Blautia abundance post-MNAM administration. Treatment with Blautia not only reversed diabetes indicators but also modulated the Th17/Treg balance and reduced inflammation, with its metabolite sodium acetate mimicking these effects through the G protein-coupled receptor 43 (GPR43) pathway. These findings suggest that MNAM’s mitigation of diabetes operates through modulation of the gut microbiota and immune regulation, highlighting Blautia and its metabolite as potential therapeutic agents and providing a theoretical foundation for novel treatment strategies in T2DM.
期刊介绍:
Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics.
The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process.
All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review.
While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.