Document Detail


Increasing peripheral insulin sensitivity by protein tyrosine phosphatase 1B deletion improves control of blood pressure in obesity.
MedLine Citation:
PMID:  23045458     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (K(db)H(PTP)) with mice lacking protein tyrosine phosphatase 1B (insulin desensitizer, H(db)K(PTP)) to generate obese insulin-sensitive mice (K(db)K(PTP)). BP was recorded in lean (H(db)H(PTP), H(db)K(PTP)) and obese (K(db)H(PTP), K(db)K(PTP)) 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 (H(db)H(PTP): 116 ± 2 mm Hg; K(db)H(PTP): 129 ± 4 mm Hg; K(db)K(PTP): 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, H(db)H(PTP)) were corrected in K(db)K(PTP) (112 ± 39 versus 422 ± 159 μg/d, K(db)H(PTP)), 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.
Authors:
Eric J Belin de Chantemèle; Mohammed Irfan Ali; James D Mintz; William E Rainey; Michel L Tremblay; David J Fulton; David W Stepp
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  Hypertension     Volume:  60     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-18     Completed Date:  2013-01-10     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1273-9     Citation Subset:  IM    
Affiliation:
Vascular Biology Center, Georgia Health Sciences University, Augusta, GA 30912, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-1 Receptor Agonists / pharmacology
Albuminuria / genetics,  physiopathology
Aldosterone / blood
Animals
Blood Pressure / drug effects,  genetics*,  physiology
Dose-Response Relationship, Drug
Female
Ganglionic Blockers / pharmacology
Heart Rate / genetics,  physiology
Hypertension / genetics,  physiopathology
Hypertrophy
Insulin Resistance / genetics*
Kidney Glomerulus / metabolism,  pathology,  physiopathology
Male
Mecamylamine / pharmacology
Mesenteric Arteries / drug effects,  physiopathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity / genetics*,  physiopathology
Phenylephrine / pharmacology
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / deficiency,  genetics*
Receptors, Leptin / deficiency,  genetics
Sympathetic Nervous System / drug effects,  physiopathology
Vasoconstriction / drug effects
Grant Support
ID/Acronym/Agency:
R01 HL092446/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic alpha-1 Receptor Agonists; 0/Ganglionic Blockers; 0/Receptors, Leptin; 52-39-1/Aldosterone; 59-42-7/Phenylephrine; 60-40-2/Mecamylamine; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 1
Comments/Corrections

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