[Red cell Na+/H+ exchange and role of protein kinase C in its stimulation in diabetes mellitus, essential hypertension and nephropathy].
Na+/H+ exchange (NHE) was measured as maximal initial velocity of pH-dependent H+ efflux from red cells into an alkaline medium containing Na+ in patients with insulin-dependent or noninsulin-dependent diabetes, with and without hypertension and in normoglycemic, essential hypertensives and normal controls (50 subjects in each subgroup). Maximal velocities of NHE were found in microalbuminuric patients in all subgroups, and NHE correlated with the rate of micro-albuminuria (r = 0.61, p = 0.02). Daily insulin requirements were greater in those with elevated NHE (84 +/- 8 vs 42 +/- 4 U/day). There was no correlation between NHE and levels of plasma glucose, HbA1 and plasma aldosterone and lipid profile and PRA. NHE was correlated with plasma prolactin (r = 0.51, p = 0.02) and PTH r = 0.24, p = 0.05). In uremic patients, NHE was inversely correlated with creatinine clearance (r = -0.48, p = 0.03). Since calphostin C, a selective inhibitor of protein kinase C, lowered increased NHE in vitro, the protein kinase C-dependent pathway of the exchanger regulation was concluded to be responsible for NHE activation in diabetes mellitus and essential hypertension.
Koren
V
V
Dept. of Medicine C, Chaim Sheba Medical Center, Tel Hashomer.
Koldanov
R
R
Peleg
E
E
Izsak
E
E
Berezin
M
M
Rosenthal
T
T
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003925:Diabetic Angiopathies / Q000097:blood*; D003928:Diabetic Nephropathies / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000097:blood*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000097:blood*; D012964:Sodium / Q000097:blood; D017923:Sodium-Hydrogen Exchangers / Q000097:blood*; D014511:Uremia / Q000097:blood
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D017923:Sodium-Hydrogen Exchangers; C061465:calphostin complex; D012964:Sodium; D011493:Protein Kinase C