Low Ca(2+) pump activity in diabetic nephropathy.
Am J Kidney Dis
; 38(3): 465-72, 2001 Sep.
Article
em En
| MEDLINE
| ID: mdl-11532676
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 Ca(2+) pump share similar regulatory pathways, but whether abnormalities in Ca(2+) metabolism characterize DN is not known. We investigated Ca(2+) efflux rates, NHE activity, cytosolic Ca(2+) ([Ca(2+)](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. Ca(2+) pump-mediated Ca(2+) 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 Ca(2+) pump activity and NHE rates could be shown. Adjustment for glycated hemoglobin and plasma lipid levels did not affect these findings. Finally, [Ca(2+)](i) concentrations and pH(i) were normal in all patients. Low Ca(2+) pump activity is a concomitant event of elevated NHE rates in DN; the molecular dysfunction(s) underlying these abnormalities remains to be established.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sódio
/
Cálcio
/
Diabetes Mellitus Tipo 1
/
Nefropatias Diabéticas
/
Nitrogênio
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article