Role of Glucose Metabolism and Mitochondrial Function in Diabetic Kidney Disease

2021 ◽  
Vol 21 (2) ◽  
Author(s):  
Robert C. Stanton
2017 ◽  
Vol 312 (6) ◽  
pp. F951-F962 ◽  
Author(s):  
Josef G. Heuer ◽  
Shannon M. Harlan ◽  
Derek D. Yang ◽  
Dianna L. Jaqua ◽  
Jeffrey S. Boyles ◽  
...  

Transforming growth factor-alpha (TGFA) has been shown to play a role in experimental chronic kidney disease associated with nephron reduction, while its role in diabetic kidney disease (DKD) is unknown. We show here that intrarenal TGFA mRNA expression, as well as urine and serum TGFA, are increased in human DKD. We used a TGFA neutralizing antibody to determine the role of TGFA in two models of renal disease, the remnant surgical reduction model and the uninephrectomized (uniNx) db/db DKD model. In addition, the contribution of TGFA to DKD progression was examined using an adeno-associated virus approach to increase circulating TGFA in experimental DKD. In vivo blockade of TGFA attenuated kidney disease progression in both nondiabetic 129S6 nephron reduction and Type 2 diabetic uniNx db/db models, whereas overexpression of TGFA in uniNx db/db model accelerated renal disease. Therapeutic activity of the TGFA antibody was enhanced with renin angiotensin system inhibition with further improvement in renal parameters. These findings suggest a pathologic contribution of TGFA in DKD and support the possibility that therapeutic administration of neutralizing antibodies could provide a novel treatment for the disease.


1993 ◽  
Vol 22 (5) ◽  
pp. 722-726 ◽  
Author(s):  
Derek LeRoith ◽  
Haim Werner ◽  
Moshe Phillip ◽  
Charles T. Roberts

Nephron ◽  
2017 ◽  
Vol 137 (2) ◽  
pp. 137-147 ◽  
Author(s):  
Vikram Thakur ◽  
Syeda Nargis ◽  
Mayra Gonzalez ◽  
Swetak Pradhan ◽  
Daniel Terreros ◽  
...  

2009 ◽  
Vol 65 (10) ◽  
pp. 2108-2117 ◽  
Author(s):  
Allison F. Williams ◽  
Elizabeth Manias ◽  
Rowan Walker

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