Insulin modulation of Na+/Li+ countertransport: impact on hypertension and diabetes

Mitzy Canessa, Gianpaolo Zerbini

Research output: Contribution to journalArticlepeer-review


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 the Km for Na+ to activate Na/H and Na/Li EXC. Insulin also modulated the activity of Na/Li EXC in vivo because the Km for Na was significantly higher in the fed than in the fasted state. In the fed state the high Km for Na+ caused an incomplete saturation of Li+ efflux between 70 and 150 mM Na+ which led to underestimation of the Vmax and Km. To correctly determine the Vmax and Km 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 higher Km and Vmax 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.

Original languageEnglish
Pages (from-to)186-190
Number of pages5
JournalActa Diabetologica
Issue number3-4
Publication statusPublished - Sep 1992


  • Diabetes
  • Hypertension
  • Insulin
  • Red blood cell
  • Sodium-lithium countertransport
  • Sodium-proton exchange

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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