Increasing peripheral insulin sensitivity by protein tyrosine phosphatase 1B deletion improves control of blood pressure in obesity

Eric J.Belin De Chantemèle, Mohammed Irfan Ali, James D. Mintz, William E. Rainey, Michel L. Tremblay, David J. Fulton, David W. Stepp

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Obesity is a major risk factor for hypertension. The copresentation of hypertension and insulin resistance (IR) suggests a role for IR in blood pressure (BP) dysregulation. To test this hypothesis, peripheral IR has been genetically subtracted in a model of obesity by crossing leptin receptor mutant mice (KdbHPTP) with mice lacking protein tyrosine phosphatase 1B (insulin desensitizer, HdbKPTP) to generate obese insulin-sensitive mice (KdbKPTP). BP was recorded in lean (HdbHPTP, HdbKPTP) and obese (KdbHPTP, KdbKPTP) mice via telemetry, and a frequency analysis of the recording was performed to determine BP variability. Correction of IR in obese mice normalized BP values to baseline levels (HdbHPTP: 116±2 mm Hg; KdbHPTP: 129±4 mm Hg; KdbKPTP: 114±5 mm Hg) and restored BP variability by decreasing its standard deviation and the frequency of BP values over the upper autoregulatory limit of the kidneys. However, although IR-induced increases in proteinuria (versus 53±13 μg/d, HdbHPTP) were corrected in KdbKPTP (112±39 versus 422±159 μg/d, KdbHPTP), glomerular hypertrophy was not. IR reduced plasma aldosterone levels ruling out a role for mineralocorticoids in the development of hypertension. Taken together, these data indicate that correction of IR prevents hypertension, BP variability, and microalbuminuria in obese mice. Although the mechanism remains to be fully determined, increases in aldosterone or sympathoactivation of the cardiovascular system seem to be less likely contributors.

Original languageEnglish (US)
Pages (from-to)1273-1279
Number of pages7
JournalHypertension
Volume60
Issue number5
DOIs
StatePublished - Nov 1 2012

Keywords

  • aldosterone
  • db/db mice
  • obese mice
  • pressure variability

ASJC Scopus subject areas

  • Internal Medicine

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