Summary
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 antihyper-tensive 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/1, 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/1; 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. These results demonstrate that plasma concentration of OLI is closely associated with the severity of IR but not with blood pressure elevation. It is, however, possible that in some fraction of NIDDM patients with insulin resistance, the elevation of blood pressure may be causally related to circulating OLI.
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Abbreviations
- BSA:
-
Bovine serum albumin
- NIDDM:
-
non-insulin-dependent diabetes mellitus
- OLI:
-
ouabain-like immunoreactivity
- GIR:
-
glucose infusion rate
- BMI:
-
body mass index
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Part of this study was presented in the 54th Annual Meeting of the American Diabetes Association, June 11-14, 1994, New Orleans, USA
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Wasada, T., Kuroki, H., Naruse, M. et al. Insulin resistance is associated with high plasma ouabain-like immunoreactivity concentration in NIDDM. Diabetologia 38, 792–797 (1995). https://doi.org/10.1007/s001250050354
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DOI: https://doi.org/10.1007/s001250050354