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Na/Li countertransport abnormalities in type 1 diabetes with and without nephropathy are familial

Lookup NU author(s): Professor Robert Wilkinson, Dr Trevor Thomas


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OBJECTIVE - To determine whether there is a familial abnormality in erythrocyte Na/Li countertransport (CT) kinetics in the approximate one-third of type 1 diabetic patients that succumb to a familial predisposition to nephropathy. RESEARCH DESIGN AND METHODS - Erythrocyte Na/Li CT kinetics were measured in nondiabetic first-degree relatives of type 1 diabetic patients with nephropathy (DNrel) (n = 32) or without nephropathy (DCrel) (n = 22) and normal control subjects ( n = 25). RESULTS - increases in outside-site Na ion association rate constant and turnover rate of Na/Li countertransport (CT) in DNrels caused increases in V-max/K-m and V-max, respectively. Thiol alkylation with N-ethylmaleimide (NEM) modifies these kinetic parameters abnormally in nephropathy. With Na ions at the outside site of the transporter, thiol alkylation causes a large decrease in V-max; but in their absence, V-max, is decreased in normal control subjects, unchanged in DCrels, or increased in DNrels. The relationship between V-max values after thiol alkylation with or without Na ions was different in DNrels (P < 0.001). Kinetic parameters with and without thiol alkylation identified 60% of DNrels and 20% of DCrels as abnormal. The single-flux rate assay of Na/Li CT did not give this discrimination, and its use may cause discrepancy between studies. CONCLUSIONS - Clinically normal untreated DNrels have the same abnormality in Na/Li CT as the affected patients. DNrels had a metabolic syndrome with increased BMI and plasma triglycerides, bur no elevation in blood pressure. Na/Li CT can detect those type 1 diabetic patients at risk of nephropathy who have a familial abnormality in a membrane thiol protein.

Publication metadata

Author(s): Thomas TH; Wilkinson R; Mead PA

Publication type: Article

Publication status: Published

Journal: Diabetes Care

Year: 2001

Volume: 24

Issue: 3

Pages: 527-532

ISSN (print): 0149-5992

ISSN (electronic): 1935-5548

Publisher: American Diabetes Association


DOI: 10.2337/diacare.24.3.527


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