Impaired insulin clearance in essential hypertension.
The purpose of this study was to examine whether impaired insulin clearance contributes to the hyperinsulinemia observed in humans with essential hypertension. Previous studies from our group and others have demonstrated that individuals with essential hypertension are resistant to the glucoregulatory effect of insulin. Animal models have confirmed this finding and have suggested that hypertensive animals have impaired insulin clearance that might contribute to the observed hyperinsulinemia. The metabolic clearance rate of insulin (MCRins) was calculated during a constant infusion of glucose (320 mg/m2/min) and insulin (25 mU/m2/min), under conditions where endogenous insulin secretion was suppressed by somatostatin infusion (250 micrograms/h) for four groups of age sex and weight-matched patients: normotensive volunteers, untreated hypertensives, hypertensives treated with diuretics and hypertensives treated with diuretics and beta-blockers. MCRins was impaired in all three groups of hypertensive subjects compared with normal BP volunteers, particularly in untreated hypertensives and those treated with combination diuretic and beta-blocker therapy: normal = 0.6 +/- 0.1; untreated = 0.47 +/- 0.2; diuretic = 0.51 +/- 0.1; combination = 0.39 +/- 0.2 (in ml/min, expressed as mean +/- SD). The effectiveness of somatostatin for islet suppression was confirmed by demonstrating markedly diminished C-peptide concentrations in untreated hypertensives and normal volunteers. Thus, our previous finding of elevated steady-state plasma insulin during insulin suppression testing in hypertensives seems not to be the result of impaired pancreatic response to somatostatin but, rather, there seems to be a defect in insulin clearance in these individuals not unlike that demonstrated in animal models of hypertension and insulin resistance. The nature of this defect remains to be elucidated.
Swislocki
A L
AL
Medical Service, Department of Veterans Affairs Medical Center, Martinez, CA 94553.
D000328:Adult; D000368:Aged; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013004:Somatostatin / Q000502:physiology
D007328:Insulin; D013004:Somatostatin