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Effect of protein kinase C modulators on the leucocyte Na+/H+ antiport in Type 1 (insulin-dependent) diabetic subjects with albuminuria

Summary

It is uncertain why only one third of Type 1 (insulin-dependent) diabetic patients develop nephropathy. One suggestion is the inheritance of a predisposition to essential hypertension. We have previously found elevated Na+/H+ antiport activity and a raised intracellular pH in leucocytes from hypertensive and Type 1 diabetic subjects with albuminuria using a novel double ionophore fluorimetric technique. These changes are not found in Type 1 diabetic subjects without albuminuria. We wished to test the effect of a protein kinase C inhibitor staurosporine (100 nmol/l) on the elevated antiport activity, and the degree of stimulation achieved by exogenous diacyl glycerol. Raised leucocyte Na+/H+ antiport activity of Type 1 diabetic subjects with albuminuria (73.8±17.2 mmol·l−1·min−1) was restored to normal levels with staurosporine (54.9±17.9 mmol·l−1·min−1, p<0.001). The leucocyte Na+/H+ antiport activity of diabetic subjects without albuminuria fell significantly also with staurosporine but to a lesser extent (57.3±11.6 to 50.0±12.8 mmol/l, p<0.003). In contrast, leucocytes from normal control subjects showed no change in antiport activity with staurosporine (54.3±8.5 to 52.6±10.4 mmol ·1−1·min−1). Dioctanoyl glycerol stimulated the leucocyte Na+/H+ antiport in normal subjects and diabetic patients without albuminuria, with significantly less stimulation in diabetic patients with albuminuria. We conclude that reversal by staurosporine of the elevated Na+/H+ antiport activity in Type 1 diabetic subjects with albuminuria could indicate a role for protein kinase C in activating the antiport. This hypothesis is supported by the reduced stimulation of the antiport by dioctanoyl glycerol in this group of patients.

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Ng, L.L., Simmons, D., Frighi, V. et al. Effect of protein kinase C modulators on the leucocyte Na+/H+ antiport in Type 1 (insulin-dependent) diabetic subjects with albuminuria. Diabetologia 33, 278–284 (1990). https://doi.org/10.1007/BF00403321

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Key words

  • Sodium
  • leucocytes
  • amiloride
  • protein kinase
  • Type 1 (insulin-dependent) diabetes