Acute Effects of Blood Pressure Elevation on Insulin Clearance in Normotensive Healthy Subjects

Abstract

Abstract —Reduced clearance of insulin from plasma contributes to the hyperinsulinemia associated with essential hypertension (EH); however, the association between impaired insulin clearance and EH remains unexplained. Whether elevated blood pressure (BP) affects insulin clearance is unknown; therefore, we used the hyperinsulinemic euglycemic clamp to determine the effects of BP elevation on insulin clearance and sensitivity in eight healthy volunteers. Placebo infusion increased mean BP by 2.6±1.6 mm Hg, which was significantly less than rises produced by phenylephrine, an α 1 -adrenoceptor agonist (+11±1.8 mm Hg, P <.05), or by angiotensin II (+13±1.3 mm Hg, P <.01). Although β-adrenoceptor stimulation with isoproterenol did not change mean BP (+3.6 mm Hg, P =NS), it significantly increased systolic pressure (+23±2.8 mm Hg versus +2.3±4.6 mm Hg with placebo P <.01). Insulin secretion (ie, C-peptide concentrations) was not affected by any of the treatments; however, phenylephrine significantly reduced the metabolic clearance rate of insulin (MCR insulin ) (16.6±1.0 mL/kg per minute with placebo versus 13.6±0.7 mL/kg per minute with phenylephrine, P <.01) and thereby increased plasma insulin concentrations (66±5.1 μU/mL with placebo versus 79±4.1 μU/mL with phenylephrine, P <.05). Phenylephrine also increased glucose utilization (42±5.8 μmol/kg per minute during placebo versus 58±4.8 μmol/kg per minute during phenylephrine, P <.05); however, this was proportional to the increased insulin concentrations; therefore, insulin sensitivity was unchanged. MCR insulin and plasma insulin concentrations were not affected by angiotensin II; however, glucose utilization increased to 51±2.7 μmol/kg per minute ( P <.01 versus placebo), indicating insulin sensitivity was increased. MCR insulin was unaffected by isoproterenol. Thus, α-adrenergic stimulation but not increased BP per se is a potent regulator of insulin clearance and plasma insulin concentrations.