The human glomerular podocyte is a novel target for insulin action

R J M Coward, G I Welsh, J Yang, C Tasman, R Lennon, A Koziell, S Satchell, G D Holman, D Kerjaschki, J M Tavare, P W Mathieson, M A Saleem

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Abstract

Microalbuminuria is significant both as the earliest stage of diabetic nephropathy and as an independent cardiovascular risk factor in nondiabetic subjects, in whom it is associated with insulin resistance. The link between disorders of cellular insulin metabolism and albuminuria has been elusive. Here, we report using novel conditionally immortalized human podocytes in vitro and human glomeruli ex vivo that the podocyte, the principal cell responsible for prevention of urinary protein loss, is insulin responsive and able to approximately double its glucose uptake within 15 min of insulin stimulation. Conditionally immortalized human glomerular endothelial cells do not respond to insulin, suggesting that insulin has a specific effect on the podocyte in the glomerular filtration barrier. The insulin response of the podocyte occurs via the facilitative glucose transporters GLUT1 and GLUT4, and this process is dependent on the filamentous actin cytoskeleton. Insulin responsiveness in this key structural component of the glomerular filtration barrier may have central relevance for understanding of diabetic nephropathy and for the association of albuminuria with states of insulin resistance.
Original languageEnglish
Pages (from-to)3095-3102
Number of pages8
JournalDiabetes
Volume54
Issue number11
Publication statusPublished - 2005

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Podocytes
Insulin
Glomerular Filtration Barrier
Albuminuria
Diabetic Nephropathies
Insulin Resistance
Facilitative Glucose Transport Proteins
Actin Cytoskeleton
Endothelial Cells
Glucose

Cite this

Coward, R. J. M., Welsh, G. I., Yang, J., Tasman, C., Lennon, R., Koziell, A., ... Saleem, M. A. (2005). The human glomerular podocyte is a novel target for insulin action. Diabetes, 54(11), 3095-3102.

The human glomerular podocyte is a novel target for insulin action. / Coward, R J M; Welsh, G I; Yang, J; Tasman, C; Lennon, R; Koziell, A; Satchell, S; Holman, G D; Kerjaschki, D; Tavare, J M; Mathieson, P W; Saleem, M A.

In: Diabetes, Vol. 54, No. 11, 2005, p. 3095-3102.

Research output: Contribution to journalArticle

Coward, RJM, Welsh, GI, Yang, J, Tasman, C, Lennon, R, Koziell, A, Satchell, S, Holman, GD, Kerjaschki, D, Tavare, JM, Mathieson, PW & Saleem, MA 2005, 'The human glomerular podocyte is a novel target for insulin action', Diabetes, vol. 54, no. 11, pp. 3095-3102.
Coward RJM, Welsh GI, Yang J, Tasman C, Lennon R, Koziell A et al. The human glomerular podocyte is a novel target for insulin action. Diabetes. 2005;54(11):3095-3102.
Coward, R J M ; Welsh, G I ; Yang, J ; Tasman, C ; Lennon, R ; Koziell, A ; Satchell, S ; Holman, G D ; Kerjaschki, D ; Tavare, J M ; Mathieson, P W ; Saleem, M A. / The human glomerular podocyte is a novel target for insulin action. In: Diabetes. 2005 ; Vol. 54, No. 11. pp. 3095-3102.
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AB - Microalbuminuria is significant both as the earliest stage of diabetic nephropathy and as an independent cardiovascular risk factor in nondiabetic subjects, in whom it is associated with insulin resistance. The link between disorders of cellular insulin metabolism and albuminuria has been elusive. Here, we report using novel conditionally immortalized human podocytes in vitro and human glomeruli ex vivo that the podocyte, the principal cell responsible for prevention of urinary protein loss, is insulin responsive and able to approximately double its glucose uptake within 15 min of insulin stimulation. Conditionally immortalized human glomerular endothelial cells do not respond to insulin, suggesting that insulin has a specific effect on the podocyte in the glomerular filtration barrier. The insulin response of the podocyte occurs via the facilitative glucose transporters GLUT1 and GLUT4, and this process is dependent on the filamentous actin cytoskeleton. Insulin responsiveness in this key structural component of the glomerular filtration barrier may have central relevance for understanding of diabetic nephropathy and for the association of albuminuria with states of insulin resistance.

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