caa a22 4500 46912833X CHVBK 20180323133156.0 cr unu---uuuuu 170328e19920901xx s 000 0 eng 10.1007/BF00573486 doi (NATIONALLICENCE)springer-10.1007/BF00573486 Insulin modulation of Na+/Li+ countertransport: impact on hypertension and diabetes [Elektronische Daten] [Mitzy Canessa, Gianpaolo Zerbini] The presence in human red blood cells (RBC) of insulin receptors led us to examine the role of insulin in the regulation of Na/Li and Na/H exchanges (EXCs) that we previously reported to have high activity in hypertension and diabetic nephropathy. To this end, red cells of fasted normotensive subjects were incubated for 1 h with insulin (0-100 μU/ml) to study the external Na+ activation at ten Na+ concentrations. We found that insulin increased twofold theK m for Na+ to activate Na/H and Na/Li EXC. Insulin also modulated the activity of Na/Li EXC in vivo because theK m for Na was significantly higher in the fed than in the fasted state. In the fed state the highK m for Na+ caused an incomplete saturation of Li+ efflux between 70 and 150 mM Na+ which led to underestimation of theV max andK m. To correctly determine theV max andK m for the extracellular Na+ of Na/Li EXC it is critical to control the feeding status of cases and controls and to ensure complete saturation of the flux. We have studied the Na+-activation kinetics of Na/Li EXC in fed normoalbuminuric and nephropathic patients, raising Na+ concentrations up to 280 mM under isosmotic conditions to avoid cell shrinkage. Under such conditions, Na/Li EXC shows significantly higherK m andV max values in nephropathic than in normoalbuminuric patients; this finding may explain the different results obtained by others in fed diabetic patients. The kinetic alterations of Na/Li EXC are also shared by patients with insulin-resistant hypertension as well as by red blood cells of fasted control subjects exposed in vitro to insulin action. We propose, therefore, that hyperinsulinaemia and/or a hyper-responsiveness of this Na+ antiporter to insulin are linked to the phenotypic alterations of Na/Li EXC in diabetes and hypertension. Springer-Verlag, 1992 Diabetes nationallicence Hypertension nationallicence Insulin nationallicence Red blood cell nationallicence Sodium-lithium countertransport nationallicence Sodium-proton exchange nationallicence Canessa Mitzy Endocrine-Hypertension Division, Brigham and Women's Hospital, 221 Longwood Avenue, 02115, Boston, MA, USA aut Zerbini Gianpaolo Department of Medicine, Harvard Medical School, 02115, Boston, MA, USA aut Acta Diabetologica Springer-Verlag 29/3-4(1992-09-01), 186-190 0940-5429 29:3-4<186 1992 29 592 https://doi.org/10.1007/BF00573486 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00573486 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Canessa Mitzy Endocrine-Hypertension Division, Brigham and Women's Hospital, 221 Longwood Avenue, 02115, Boston, MA, USA aut NATIONALLICENCE 700 1- Zerbini Gianpaolo Department of Medicine, Harvard Medical School, 02115, Boston, MA, USA aut NATIONALLICENCE 773 0- Acta Diabetologica Springer-Verlag 29/3-4(1992-09-01), 186-190 0940-5429 29:3-4<186 1992 29 592 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer