title: Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes.
abstract: OBJECTIVE
  Cardiac natriuretic peptides (NPs) bind to two receptors (NPRA-mediator of signaling; NPRC-clearance receptor) whose ratio, NPRR (NPRA/NPRC), determines the NP bioactivity. This study investigated the relationship of NP receptor gene expression in adipose tissue and muscle with obesity and glucose intolerance. Prospectively, the study also assessed whether changes in NP receptor expression and thermogenic gene markers accompanied improvements of insulin sensitivity.
  
  
  METHODS
  A cross-sectional study of subjects with a wide range of BMI and glucose tolerance (n = 50) was conducted, as well as a randomized 12-week trial of subjects with type 2 diabetes mellitus (T2DM) treated with pioglitazone (n = 9) or placebo (n = 10).
  
  
  RESULTS
  NPRR mRNA was significantly lower in adipose tissue of subjects with obesity when compared with lean subjects (P ≤ 0.001). NPRR decreased with progression from normal glucose tolerance to T2DM (P < 0.01) independently of obesity. Treatment of subjects with T2DM with pioglitazone increased NPRR in adipose tissue (P ≤ 0.01) in conjunction with improvements in insulin sensitivity and increases of the thermogenic markers PPARγ coactivator-1α and uncoupling protein 1 (P ≤ 0.01).
  
  
  CONCLUSIONS
  Decreased adipose tissue NPRR was associated with obesity, glucose intolerance, and insulin resistance. This relationship was not observed for skeletal muscle NPRR. Pharmacological improvement of insulin sensitivity in subjects with T2DM was tied to improvement in NPRR and increased expression of genes involved in thermogenic processes.
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida, USA.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kovacova
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Tharp
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida, USA.
authors.forename: Dianxin
authors.initials: D
authors.lastname: Liu
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida, USA.
authors.forename: Wan
authors.initials: W
authors.lastname: Wei
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Collins
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida, USA.|Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pratley
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D000077205:Pioglitazone; D017461:Receptors, Atrial Natriuretic Factor / Q000032:analysis / Q000378:metabolism; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D017461:Receptors, Atrial Natriuretic Factor; D000077205:Pioglitazone
keywords: adipose tissue; natriuretic peptide receptors; obesity; type 2 diabetes mellitus