Insulin resistance is associated with high plasma ouabain-like immunoreactivity concentration in NIDDM

Abstract

The aim of the present study was to elucidate the pathophysiologic significance of circulating ouabain as a link between insulin resistance (IR) and hypertension (HT) in NIDDM. Euglycaemic (4.5 mmol/l) hyperinsulinaemic (360-580 pmol/l) clamping was performed using an artificial endocrine pancreas. Plasma ouabain-like immunoreactivity (OLI) was determined by radioimmunoassay using a highly specific antibody to ouabain. HT was defined as systolic blood pressure > 140 mm Hg and/or diastolic > 90 mm Hg or being treated with antihypertensive agents. The values (mean +/- SEM) of glucose infusion rate (GIR) and plasma OLI were compared among the four groups classified using IR and HT as factors. Group I (IR-/HT-, n = 15): GIR 7.20 +/- 0.36 mg.kg-1.min-1, OLI 130.8 +/- 20.9 pmol/l, which was not different from that in eight normal control subjects (7.69 +/- 0.40 mg.kg-1.min-1 and 142.6 +/- 32.3 pmol/l, respectively); Group II (IR-/HT+, n = 13): 5.89 +/- 0.36 mg.kg-1.min-1, 172.5 +/- 35.0 pmol/l; Group III (IR+/HT-, n = 14) 1.91 +/- 0.28 mg.kg-1.min-1, 576.6 +/- 161.5 pmol/l (p < 0.01 vs Group I and II); Group IV (IR+/HT+, n = 15) 1.79 +/- 0.22 mg.kg-1.min-1, 703.1 +/- 170.1 pmol/l (p < 0.01 vs Group I and II), respectively. Six of 57 NIDDM patients studied exhibited very high (> 1500 pmol/l) plasma OLI concentrations, showed marked insulin resistance and were all hypertensive. When analysed as a whole, plasma OLI was negatively correlated with GIR (p < 0.001), but was not correlated with arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)