Department of Surgery, State University of New York (SUNY), Upstate Medical University, 750 E Adams St., Suite 8141, Syracuse, NY, 13210, USA.
Department of Pathology, State University of New York (SUNY), Upstate Medical University, Syracuse, NY, USA.
Sci Rep. 2023 Sep 20;13(1):15544. doi: 10.1038/s41598-023-42665-2.
Galantamine, a centrally acting acetylcholinesterase inhibitor, has been shown to attenuate inflammation and insulin resistance in patients with metabolic syndrome. We investigated the effects of galantamine on glycemic control and development of diabetic nephropathy (DN) in Lepr mice. Galantamine significantly reduced food intake, body weight, blood glucose and HbA1c levels. Insulin resistance (HOMA-IR, QUICKI), HOMA-β and elevations in plasma inflammatory cytokine levels (TNF-α, IL-6 and HMGB-1) were all attenuated by galantamine. Galantamine also ameliorated diabetes-induced kidney injury as evidenced by improvements in renal function (BUN, creatinine, albuminuria), histologic injury and apoptosis. Improved glycemic control and nephropathy were associated with increased circulating GLP-1, decreased renal P-38 MAPK and caspase-1 activation and reduced SGLT-2 expression. These findings provide insights into the mechanisms by which galantamine improves glycemic control and attenuates DN in the Lepr mouse model.
加兰他敏是一种中枢作用的乙酰胆碱酯酶抑制剂，已被证明可减轻代谢综合征患者的炎症和胰岛素抵抗。我们研究了加兰他敏对 Lepr 小鼠血糖控制和糖尿病肾病 (DN) 发展的影响。加兰他敏可显著降低食物摄入量、体重、血糖和 HbA1c 水平。胰岛素抵抗 (HOMA-IR、QUICKI)、HOMA-β 和血浆炎症细胞因子水平 (TNF-α、IL-6 和 HMGB-1) 的升高均被加兰他敏减弱。加兰他敏还改善了糖尿病引起的肾脏损伤，表现为肾功能 (BUN、肌酐、蛋白尿)、组织学损伤和细胞凋亡的改善。血糖控制的改善和肾病的减轻与循环 GLP-1 的增加、肾 P-38 MAPK 和 caspase-1 激活的减少以及 SGLT-2 表达的减少有关。这些发现为加兰他敏改善 Lepr 小鼠模型中的血糖控制和减轻 DN 的机制提供了新的见解。
