Erythrocyte sodium-lithium countertransport activity is related to membrane fluidity in IDDM patients.
Sodium-lithium countertransport (SLC) activity at a standard physiological sodium concentration is raised in uncomplicated IDDM, for which the kinetic mechanism is a raised maximum velocity (Vmax). Diabetic patients with nephropathy do not have raised values for Vmax but a low Michaelis constant (km). Transporter activity could be influenced by its membrane lipid environment. This was assessed in 21 control subjects, 32 uncomplicated diabetic patients, 17 patients with diabetic nephropathy and 11 patients with non-diabetic nephropathy by measuring the fluorescence anisotropy of DPH and TMA-DPH to assess different membrane regions. Standard SLC was higher in all the patient groups compared to the control subjects: 0.307 +/- 0.020 mmol Li/h x 1 cells in uncomplicated IDDM; 0.300 +/- 0.032 in diabetic nephropathy patients and 0.276 +/- 0.019 in non-diabetic nephropathy patients vs 0.216 +/- 0.011 mmol Li/h x 1 cells in control subjects (p < 0.001, p < 0.05, p < 0.05, respectively). This was due to raised Vmax values in the uncomplicated group: 0.528 +/- 0.035 vs 0.385 +/- 0.022 mmol Li/h x 1 cells in control subjects (p = 0.001) and low values for km in the diabetic nephropathy group: 58 (27-170) vs 106 (81-161) mmol/l in control subjects (p < 0.001). Raised SLC in the non-diabetic nephropathy group was largely due to raised Vmax: 0.460 +/- 0.030 mmol Li/h x 1 cells; p = 0.053, with no difference in km: 99.5 (74-137).(ABSTRACT TRUNCATED AT 250 WORDS)
Dowd
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A
Department of Nephrology, Freeman Hospital, Newcastle upon Tyne, UK.
Thomas
T H
TH
Taylor
R
R
Wilkinson
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R
D000328:Adult; D001692:Biological Transport; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism; D004161:Diphenylhexatriene / Q000031:analogs & derivatives / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005260:Female; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D006801:Humans; D008094:Lithium / Q000378:metabolism*; D008297:Male; D008560:Membrane Fluidity / Q000502:physiology*; D008875:Middle Aged; D012964:Sodium / Q000378:metabolism*
D005456:Fluorescent Dyes; D004161:Diphenylhexatriene; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; D008094:Lithium; D012964:Sodium