Glucose Transporter Roles in the Development of Glomerulosclerosis

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Charles W. Heilig Alaa Awad Irtiza Hasan Ali Rawabdeh Yongxin Gao Vishal Jaikaransingh


Extensive research has been done over the last several decades in pursuit of mechanisms leading to the glomerular disease and glomerulosclerosis in diabetic nephropathy. Much of the research investigated downstream pathways and terminal pathways to extracellular matrix production in the mesangial cells, after exposure to diabetes mellitus or high extracellular glucose concentrations. More recent research identified glucose transporter proteins expressed in normal and diabetic glomeruli, with the potential to regulate glucose uptake and metabolism in the glomerular mesangial cells. The mesangial cells are directly involved in excess matrix production in both diabetic and nondiabetic glomerulosclerosis. The common finding of excess glomerular glucose transporter expression in the development of both diabetic and nondiabetic glomerulosclerosis, provides a clue to how these glomerular lesions develop. Here, we review the potential roles of glucose transporter proteins, particularly facilitative glucose transporters (GLUTs), in enhancing mesangial cell glucose uptake, metabolism, and signaling to extracellular matrix expression which scars glomeruli. Both diabetes mellitus and glomerular hypertension without diabetes, have been shown to stimulate glomerular GLUT1 expression allowing for increased cellular glucose uptake. The stretch – inducible Mechano-Growth Factor recently identified in mesangial cells has the potential to translate glomerular hypertension with mesangial stretch in both diabetic and nondiabetic glomerular disease, into excess mesangial GLUT1 expression, glucose uptake and matrix production. Future research on this topic will likely be valuable. Positive feedback mechanisms are highlighted which can enhance mesangial GLUT1 expression to perpetuate glucose-induced matrix production and glomerular scarring in vivo.

Keywords: Glucose Transporter, GLUT, diabetic glomerulosclerosis, nondiabetic glomerulosclerosis, mesangial cell

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HEILIG, Charles W. et al. Glucose Transporter Roles in the Development of Glomerulosclerosis. Medical Research Archives, [S.l.], v. 12, n. 3, mar. 2024. ISSN 2375-1924. Available at: <>. Date accessed: 13 apr. 2024. doi:
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