Acute effects of blood pressure elevation on insulin clearance in normotensive healthy subjects.
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 alpha1-adrenoceptor agonist (+11+/-1.8 mmHg, P<.05), or by angiotensin II (+13+/-1.3 mmHg, P<.01). Although beta-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 (MCRinsulin) (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 microU/mL with placebo versus 79+/-4.1 microU/mL with phenylephrine, P<.05). Phenylephrine also increased glucose utilization (42+/-5.8 micromol/kg per minute during placebo versus 58+/-4.8 micromol/kg per minute during phenylephrine, P<.05); however, this was proportional to the increased insulin concentrations; therefore, insulin sensitivity was unchanged. MCRinsulin and plasma insulin concentrations were not affected by angiotensin II; however, glucose utilization increased to 51+/-2.7 micromol/kg per minute (P<.01 versus placebo), indicating insulin sensitivity was increased. MCRinsulin was unaffected by isoproterenol. Thus, alpha-adrenergic stimulation but not increased BP per se is a potent regulator of insulin clearance and plasma insulin concentrations.
O'Callaghan
C J
CJ
University of Melbourne, Department of Medicine, Austin and Repatriation Medical Center, Heidelberg, Australia.
Komersova
K
K
Louis
W J
WJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D004311:Double-Blind Method; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D007328:Insulin; D000804:Angiotensin II; D010656:Phenylephrine; D007545:Isoproterenol