title: Insulin up-regulates natriuretic peptide clearance receptor expression in the subcutaneous fat depot in obese subjects: a missing link between CVD risk and obesity?
abstract: BACKGROUND
  Natriuretic peptides (NP) regulate cardiovascular homeostasis and have multiple metabolic properties. Decreased levels of NP or "natriuretic handicap" are signs of insulin resistance such as central obesity. Increased expression of NP clearance receptor (NPRC) in sc adipose tissue (SAT) was observed in insulin-resistant subjects.
  
  
  OBJECTIVE
  We hypothesized that insulin acutely regulates NP receptor expression in adipose tissue.
  
  
  METHODS
  NPRA, NPRB, and NPRC mRNA expression was measured in paired samples of visceral adipose tissue (VAT) and SAT from 157 subjects (108 with type 2 diabetes). The effect of insulin on NPR gene expression in SAT was studied in euglycemic-hyperinsulinemic and hyperglycemic-hyperinsulinemic clamp experiments. Additionally, the effect of insulin and glucose on NPR expression in the culture of primary human monocytes and macrophages was tested.
  
  
  RESULTS
  NPRA and NPRC gene expression was higher in VAT compared with SAT (P < 0.01), but only NPRC gene expression strongly correlated with fasting insulin levels (r = 0.65, P = 0.04 × 10(-3); and r = 0.54, P = 0.002, for VAT and SAT, respectively). NPRB expression was lower in VAT than in SAT in subjects with type 2 diabetes and was lower compared with nondiabetic subjects. NPRC gene expression was up-regulated in SAT during both euglycemic- and hyperglycemic-hyperinsulinemic clamps (P = 0.038 and P = 0.048, respectively), and was increased in high glucose and insulin treatment in monocytes (70.2%; P = 0.01), but not in mature macrophages.
  
  
  CONCLUSIONS
  Insulin increased expression of NPRC in SAT independently of circulating glucose concentrations. Thus, insulin might suppress circulating NP via up-regulation of NPRC expression in obesity, providing a novel link between hyperinsulinemia and obesity.
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Pivovarova
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Gögebakan
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
authors.forename: Andrea
authors.initials: A
authors.lastname: Sparwasser
authors.forename: Martin O
authors.initials: MO
authors.lastname: Weickert
authors.forename: Isam
authors.initials: I
authors.lastname: Haddad
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Nikiforova
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
authors.forename: Michael
authors.initials: M
authors.lastname: Kruse
authors.forename: Anne-Cathrin
authors.initials: AC
authors.lastname: Seltmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.forename: Natalia
authors.initials: N
authors.lastname: Rudovich
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C