INSULIN-RESISTANCE IS ASSOCIATED WITH HIGH PLASMA OUABAIN-LIKE IMMUNOREACTIVITY CONCENTRATION IN NIDDM

The aim of the present study was to elucidate the pathophysiologic sig nificance of circulating ouabain as a link between insulin resistance (IR) and hypertension (HT) in NIDDM. Euglycaemic (4.5 mmol/l) hyperins ulinaemic (360-580 pmol/l) clamping was performed using an artificial endocrine pancreas. Plasma ouabain-like immunoreactivity (OLI) was det ermined by radioimmunoassay using a highly specific antibody to ouabai n. HT was defined as systolic blood pressure > 140 mm Hg and/or diasto lic > 90 mm Hg or being treated with antihypertensive agents. The valu es (mean +/- SEM) of glucose infusion rate (GIR) and plasma OLI were c ompared among the four groups classified using IR and HT as factors. G roup 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 norm al 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 m g . kg(-1) . min(-1), pmol/l; Group III (IR+HT-, n = 14) 1.91 +/- 0.28 mg . kg(-1) . min(-1), 576.6 +/- 1.61.5 pmol/l (p < 0.01 vs Group I a nd 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. S ix of 57 NIDDM patients studied exhibited very high (> 1500 pmol/l) pl asma OLI concentrations, showed marked insulin resistance and were all hypertensive. When analysed as a whole, plasma OLI was negatively cor related with GIR (p < 0.001), but was not correlated with arterial blo od pressure. These results demonstrate that plasma concentration of OL I is closely associated with the severity of IR but not with blood pre ssure elevation. It is, however, possible that in some fraction of NID DM patients with insulin resistance, the elevation of blood pressure m ay be causally related to circulating OLI.