Titre du document / Document title

Low Ca²⁺ pump activity in diabetic nephropathy

Auteur(s) / Author(s)

PODESTA Francesca ⁽¹⁾ ; MEREGALLI Giancarla ⁽¹⁾ ; GHELARDI Renata ⁽¹⁾ ; DEL GIUDICE Rosmina ⁽¹⁾ ; ASNAGHI Veronica ⁽¹⁾ ; MAESTRONI Anna ⁽¹⁾ ; ZERBINI Gianpaolo ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Renal Pathophysiology Laboratory, Division of Medicine, Scientific Institute San Raffaele, University of Milan, Milan, ITALIE

Résumé / Abstract

○ Elevated cell Na⁺-H⁺ exchange (NHE) activity characterizes diabetic nephropathy (DN), but the mechanisms of this abnormality are unclear. Recent evidence suggests that NHE and the Ca²⁺ pump share similar regulatory pathways, but whether abnormalities in Ca²⁺ metabolism characterize DN is not known. We investigated Ca²⁺ efflux rates, NHE activity, cytosolic Ca²⁺ ([Ca²⁺]_i) concentrations, and intracellular pH (pH_i) in human skin fibroblasts from 20 patients with type 1 (insulin-dependent) diabetes and nephropathy; 20 patients with diabetes with normoalbuminuria matched for age, sex, and duration of diabetes; and 10 individuals without diabetes. Ca²⁺ pump-mediated Ca²⁺ efflux was significantly lower in patients with nephropathy than In patients with normoalbuminuria and individuals without diabetes (0.074 ± 0.01 versus 0.115 ± 0.01 versus 0.131 ± 0.02 nmol.mg_protein-1.min^-1_; analysis of variance [ANOVA], P = 0.015). Elevated maximal velocity of the Na⁺-H⁺ exchanger was confirmed In fibroblasts from patients with nephropathy (14.4 ± 1.2 versus 7.1 ± 0.7 versus 8.0 ± 1.2 mmol H⁺.l cell^-1.min^-1; ANOVA, P < 0.0001). A reverse correlation between Ca²⁺ pump activity and NHE rates could be shown. Adjustment for glycated hemoglobin and plasma lipid levels did not affect these findings. Finally, [Ca²⁺]_i concentrations and pH_i were normal in all patients. Low Ca²⁺ pump activity is a concomitant event of elevated NHE rates in DN; the molecular dysfunction(s) underlying these abnormalities remains to be established.

Revue / Journal Title

American journal of kidney diseases   ISSN 0272-6386 

Source / Source

2001, vol. 38, n^o3, pp. 465-472 (49 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Orlando, FL, ETATS-UNIS  (1981) (Revue)

Mots-clés anglais / English Keywords

Endocrinopathy ; Kidney disease ; Urinary system disease ; Human ; Exploration ; Concomitant disease ; Hydrogen ; Ion exchange ; Calcium ; Ionic channel ; Diabetes mellitus ; Nephropathy ;

Mots-clés français / French Keywords

Endocrinopathie ; Rein pathologie ; Appareil urinaire pathologie ; Homme ; Exploration ; Association morbide ; Hydrogène ; Echange ion ; Calcium ; Canal ionique ; Diabète ; Néphropathie ;

Mots-clés espagnols / Spanish Keywords

Endocrinopatía ; Riñón patología ; Aparato urinario patología ; Hombre ; Exploración ; Asociación morbosa ; Hidrógeno ; Cambio iónico ; Calcio ; Canal iónico ; Diabetes ; Nefropatía ;

Localisation / Location

INIST-CNRS, Cote INIST : 19098, 35400009918112.0020