Type 1 diabetes mellitus is characterized by immune-mediated pancreatic β-cell loss and progressive impairment of insulin production. This study evaluated the effects of combined rituximab, a B-cell-directed therapy, and exendin-4, a glucagon-like peptide-1 receptor agonist, on β-cell-related function and metabolic outcomes in experimental type 1 diabetes. Pancreatic islets isolated from NOD-scid mice were used for in vitro assessment of viability, metabolic activity, insulin secretion under high-glucose conditions, and gene expression. Female NOD mice were assigned to control, exendin-4, rituximab, or combination treatment groups and treated for approximately 20 weeks. Combined treatment showed the greatest increases in insulin-related responses in vitro. In vivo, it was associated with more stable fasting blood glucose levels, improved oral glucose tolerance, delayed progression to hyperglycemia, increased circulating insulin and C-peptide levels, and reduced glucagon, HbA1c, and LDL levels. Histological and molecular analyses further demonstrated reduced pancreatic inflammatory damage, reduced apoptosis-associated changes, and increased BrdU- and cytokeratin-18-associated signals within insulin-positive islet regions. These findings support further investigation of combined B-cell-directed and β-cell-supportive strategies for preserving islet function and delaying disease progression in type 1 diabetes.

N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic RNA, and has increasingly been recognized as a critical regulator of gene expression at both the transcriptional and post-transcriptional levels. The m6A modification process is highly dynamic and reversible, governed by methyltransferase writers (e.g., METTL3, METTL14, WTAP), demethylase erasers (such as FTO and ALKBH5), and specific readers (including YTHDF and IGF2BP protein families) that interpret the modification and mediate its downstream effects. Accumulating evidence indicates that m6A-mediated regulation of non-coding RNAs (ncRNAs) plays a pivotal role in osteogenic differentiation, a process central to bone formation. Impaired osteogenesis, which contributes to decreased bone mass, is closely linked to the onset and progression of osteoporosis. This review summarizes recent progress on the interplay between m6A modification and ncRNAs in osteogenic differentiation, and outlines a regulatory framework, the m6A-ncRNA-target gene axis, that includes m6A modification, ncRNA interactions, and downstream signaling pathways, such as Wnt/β-catenin and BMP/Smad, and discusses their potential as biomarkers or therapeutic targets for osteoporosis, with the goal of providing new insights into the epigenetic mechanisms underlying osteoporosis and to identify potential molecular targets for future therapeutic strategies.