Lee Seung-Ah, Kim Subin, Kim Seog-Young, Park Jong Yoen, Jung Hye Seung, Chung Sung Soo, Park Kyong Soo
Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea.
Diabetes Metab J. 2025 Jan;49(1):150-159. doi: 10.4093/dmj.2024.0174. Epub 2024 Oct 24.
Four soluble factors-putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102-were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45-55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.
四种可溶性因子——腐胺、氨基葡萄糖、烟酰胺以及信号转导和转录激活因子3（STAT3）抑制剂BP-1-102——已被证明在体外可将骨髓单个核细胞（BMNCs）分化为功能性胰岛素分泌细胞（IPCs）。移植这些IPCs可改善糖尿病小鼠的高血糖症状。然而，内源性BMNC再生在这一效应中的作用尚不清楚。本研究旨在评估这些因子对糖尿病小鼠体内BMNC向IPCs分化的影响。给小鼠口服这些因子，持续5天，每隔2周给药两次，并监测45 - 55天。测量葡萄糖耐量、葡萄糖刺激的胰岛素分泌以及胰腺胰岛素含量。利用携带来自胰岛素启动子荧光素酶/绿色荧光蛋白（GFP）转基因小鼠的BMNCs的嵌合小鼠来追踪内源性BMNC的命运。这些因子降低了血糖水平，改善了葡萄糖耐量，并增强了胰岛素分泌。免疫染色证实胰腺中存在IPCs，表明这些因子具有诱导β细胞再生和改善糖尿病治疗的潜力。
