Kinetic behavior of the erythrocyte sodium-lithium countertransporter in nonnephropathic diabetic twins.
Elevated erythrocyte sodium-lithium countertransport activity occurs in diabetes and may be genetically mediated. The relation of this abnormality to the disease and its complications is unclear. To remove confounding genetic factors and the impact of complications, we studied sodium-lithium countertransport activity together with its kinetic components, maximal rate of turnover (Vmax) and external affinity for sodium (kNa), in identical-twin pairs discordant for insulin-dependent diabetes who were normotensive and had no evidence of nephropathy. Fifteen twin pairs were studied along with the same number of healthy control subjects matched with the twins for gender, age, and body mass index. Clinical and laboratory characteristics of the twins and controls were similar, with the exception that whole blood glucose and glycated hemoglobin concentrations were higher in diabetic twins (P < .001). Comparison of countertransport activity between nondiabetic and diabetic twin groups failed to uncover any significant differences (P = .30, Wilcoxon). Similarly, there were no differences in countertransport activity between the nondiabetic twin group and the controls (P = .38, Mann-Whitney). Furthermore, no associations were noted between residual activity values and residual data of any of the other clinical or laboratory characteristics measured. Comparison of Vmax between nondiabetic and diabetic twin groups showed a significant elevation in the diabetic twins (0.515 + 0.220 v 0.439 + 0.229 mmol Li/L RBC x h, P = .049, paired t test). By contrast, no significant differences were noted between the nondiabetic twin group and the controls (P = .15, unpaired t test). Comparison of kNa between nondiabetic and diabetic twin groups found no significant differences in kNa (P = .42, Wilcoxon). Similarly, there were no differences in kNa between nondiabetic twins and controls (P = .14, Mann-Whitney). Neither the residual data for Vmax nor kNa showed any association with the residual data of any of the other clinical or laboratory characteristics measured. When intertwin correlations were examined, all three parameters describing the behavior of the sodium-lithium countertransporter showed significant intertwin correlations (activity, r = .51, P = .04; Vmax, r = .82, P = .001; kNa, r = .76, P = .001). In conclusion, the diabetic state has a small effect on the Vmax of the sodium-lithium countertransporter. Failure to consider the complex nature of the activity measurement is likely to have been partly responsible for earlier confusion with regard to the effect of diabetes on the countertransporter, since experimental conditions varied between studies and individual kinetic components were not measured. The associations between twins in this study with respect to Vmax and kNa indicate a genetic influence on both constants of the countertransporter. Vmax appears also to be sensitive to certain as yet unidentified environmental factors.
Hardman
T C
TC
Department of Clinical Pharmacology and Therapeutics, Charing Cross and Westminster Medical School, Chelsea and Westminster Hospital, London, UK.
Dubrey
S W
SW
Leslie
R D
RD
Lant
A F
AF
D000328:Adult; D000368:Aged; D017920:Antiporters / Q000097:blood*; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012016:Reference Values
D017920:Antiporters; C045885:sodium-lithium countertransporter