Inhibition of GLUT1 Ameliorates Thickening of the Glomerular Basement Membrane via the Rheb/mTORC1 Pathway in Diabetic Nephropathy.

Xu, Jitu; Shi, Jiaoyu; Hu, Ping; Jiang, Nan; Zhong, Jiayan; Shao, Guangze; Zhu, Siqi; Gu, Yue et al. · Diabetes · 2026

basic_science · Level V

Where this comes from

Abstract

The role of glomerular endothelial cells in basement membrane collagen α1(IV) accumulation in diabetic nephropathy was previously unclear. Glucose transporter type 1 (GLUT1) expression drives collagen α1(IV) production via Rheb upregulation and mTORC1 activation. Rheb O-GlcNAcylation serves as a key modification that activates mTORC1 signaling, leading to increased collagen α1(IV) production. Pharmacological inhibition of GLUT1 mitigates diabetic nephropathy progression, highlighting its therapeutic potential.