TY - JOUR
T1 - Na+/Li+ and Na+/H+ countertransport activity in hypertensive non- insulin-dependent diabetic patients
T2 - Role of insulin resistance and antihypertensive treatment
AU - Giordano, Mauro
AU - Castellino, Pietro
AU - Solini, Anna
AU - Canessa, Mitzy L.
AU - DeFronzo, Ralph A.
N1 - Funding Information:
From the Department of Medicine, Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio; The South Texas Veterans Healthcare System, Audie L. Murphy Division, San Antonio, TX; the Endocrine-Hypertension Division, Brigham and Women's Hospital, Boston, MA; and the Institute of Internal Medicine and Nephrology, Second University of Naples, Naples, Italy. Submitted November 18, 1997; accepted Apri128, 1997. Supported by General Clinical Research Center Grant No. MO1-RR-01346, a Veterans Affairs (VA) Merit Award, and funds from the VA Medical Research Center and GRECC, and in part by National Institutes of Health Grant No. HL-35664 and Fondecyt Grant No. 194-0339 (both to M.L.C.). Address reprint requests to Ralph A. DeFronzo, MD, The University of Texas Health Science Center at San Antonio, Department of Medicine, Diabetes Division, San Antonio, TX 78284-7886. Copyright © 1997 by W.B. Saunders Company 0026-0495/97/4611-0014503.00/0
PY - 1997
Y1 - 1997
N2 - We measured erythrocyte Na+/Li+ and Na+/H+ countertransport (CT) activity (millimoles per liter per cell per hour) in 10 healthy control subjects (age, 38 ± 4 years; body mass index, 25 ± 1 kg/m2) and in 25 hypertensive patients with non-insulin-dependent diabetes mellitus ([NIDDM] age, 49 ± 3 years; body mass index, 29 ± 1 kg/m2; fasting plasma glucose, 157 ± 12 mg/dL) 4 weeks after discontinuation of previous antihypertensive treatment. Na+/Li+ CT was significantly increased in hypertensive NIDDM patients compared with controls (0.56 ± 0.04 v 0.30 ± 0.03, P < .01), whereas Na+/H+ CT was similar to control levels (21 ± 1 v 20 ± 2). A positive correlation was found between Na+/Li+ CT and the severity of insulin resistance (r = .69, P < .01), mean arterial pressure ([MAP] r = .64, P < .01), plasma triglyceride concentration (r = .46, P < .05), and plasma total cholesterol (r = .41, P < .05). An inverse correlation was found between Na+/Li+ CT activity and plasma insulin concentration (r = -.47, P < .05). No relationship was observed between Na+/Li+ CT activity and either creatinine clearance or proteinuria. Stepwise multiple regression analysis for all metabolic variables and blood pressure showed that only the severity of insulin resistance was positively correlated with increased Na+/Li+ CT activity. Na+/H+ and Na+/Li+ CT activity were not altered by 3 hours of euglycemic physiologic hyperinsulinemia (84 ± 3 μU/mL). Hypertensive NIDDM subjects were treated for 3 months with captopril, nifedipine, or doxazosin. After captopril, e reduction of Na+/H+ CT was observed (22 ± 4 v 13 ± 2, P < .05); Na+/Li+ CT decreased after doxazosin (0.56 ± 0.06 v 0.45 ± 0.05, P < .05) and nifedipine (0.52 ± 0.06 v 0.42 ± 0.05, P < .05). In conclusion, in hypertensive NIDDM subjects, (1) Na+/Li+ CT is increased and is correlated with the level of insulin resistance and the MAP; (2) acute physiologic hyperinsulinemia does not affect Na+/Li+ or Na+/H+ CT activity; and (3) Na+/H+ CT activity is reduced by captopril, and Na+/Li+ CT is decreased by doxazosin and nifedipine.
AB - We measured erythrocyte Na+/Li+ and Na+/H+ countertransport (CT) activity (millimoles per liter per cell per hour) in 10 healthy control subjects (age, 38 ± 4 years; body mass index, 25 ± 1 kg/m2) and in 25 hypertensive patients with non-insulin-dependent diabetes mellitus ([NIDDM] age, 49 ± 3 years; body mass index, 29 ± 1 kg/m2; fasting plasma glucose, 157 ± 12 mg/dL) 4 weeks after discontinuation of previous antihypertensive treatment. Na+/Li+ CT was significantly increased in hypertensive NIDDM patients compared with controls (0.56 ± 0.04 v 0.30 ± 0.03, P < .01), whereas Na+/H+ CT was similar to control levels (21 ± 1 v 20 ± 2). A positive correlation was found between Na+/Li+ CT and the severity of insulin resistance (r = .69, P < .01), mean arterial pressure ([MAP] r = .64, P < .01), plasma triglyceride concentration (r = .46, P < .05), and plasma total cholesterol (r = .41, P < .05). An inverse correlation was found between Na+/Li+ CT activity and plasma insulin concentration (r = -.47, P < .05). No relationship was observed between Na+/Li+ CT activity and either creatinine clearance or proteinuria. Stepwise multiple regression analysis for all metabolic variables and blood pressure showed that only the severity of insulin resistance was positively correlated with increased Na+/Li+ CT activity. Na+/H+ and Na+/Li+ CT activity were not altered by 3 hours of euglycemic physiologic hyperinsulinemia (84 ± 3 μU/mL). Hypertensive NIDDM subjects were treated for 3 months with captopril, nifedipine, or doxazosin. After captopril, e reduction of Na+/H+ CT was observed (22 ± 4 v 13 ± 2, P < .05); Na+/Li+ CT decreased after doxazosin (0.56 ± 0.06 v 0.45 ± 0.05, P < .05) and nifedipine (0.52 ± 0.06 v 0.42 ± 0.05, P < .05). In conclusion, in hypertensive NIDDM subjects, (1) Na+/Li+ CT is increased and is correlated with the level of insulin resistance and the MAP; (2) acute physiologic hyperinsulinemia does not affect Na+/Li+ or Na+/H+ CT activity; and (3) Na+/H+ CT activity is reduced by captopril, and Na+/Li+ CT is decreased by doxazosin and nifedipine.
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U2 - 10.1016/S0026-0495(97)90237-7
DO - 10.1016/S0026-0495(97)90237-7
M3 - Article
C2 - 9361692
AN - SCOPUS:0030836860
SN - 0026-0495
VL - 46
SP - 1316
EP - 1323
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 11
ER -