title: Pappa2 deletion alters IGFBPs but has little effect on glucose disposal or adiposity.
abstract: OBJECTIVE
  Insulin-like growth factor binding proteins (IGFBPs) are involved in glucose and lipid metabolism, and their actions are modulated by proteases. The aim of this study was to examine the effects of an IGFBP-5 protease, pregnancy associated plasma protein-A2 (PAPP-A2), on glucose metabolism and susceptibility to diet-induced obesity.
  
  
  METHODS
  Postnatal growth, circulating IGF-I, IGFBP-3 and IGFBP-5 levels, and glucose tolerance were measured in Pappa2 deletion mice and littermate controls on a chow diet. Males were subsequently fed a high-fat diet for 8 weeks to measure weight gain and adiposity, as well as glucose tolerance in response to a metabolic challenge.
  
  
  RESULTS
  Circulating IGFBP-5 levels were ~2-fold higher in mice with no functional PAPP-A2 than in littermate controls, as expected. In contrast, circulating IGFBP-3 levels were reduced by ~15-fold, and total IGF-I levels were ~60% higher in Pappa2 deletion mice. There was no effect of Pappa2 deletion on fasting blood glucose levels or glucose clearance after intraperitoneal injection of 2g glucose/kg body weight in mice on a chow diet. In males on a high-fat diet, there was no difference between genotypes in weight gain or adiposity, adjusting for differences in initial body weight, or in fasting blood glucose or insulin levels, or in glucose clearance.
  
  
  CONCLUSIONS
  Despite a dramatic disruption of the balance between circulating IGF-I, IGFBP-3 and -5, we found no effects of Pappa2 deletion on glucose metabolism, weight gain or adiposity on a high-fat diet.
authors.affiliation: Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada. Electronic address: jkchrist@sfu.ca.
authors.forename: Julian K
authors.initials: JK
authors.lastname: Christians
authors.affiliation: Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
authors.forename: Amrit K
authors.initials: AK
authors.lastname: Bath
authors.affiliation: Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
authors.forename: Neilab
authors.initials: N
authors.lastname: Amiri
mesh_terms: D050154:Adiposity / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000172:deficiency* / Q000235:genetics; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; C000607595:IGFBP5-interacting protein, mouse; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; C514948:PAPPA2 protein, mouse; D011266:Pregnancy-Associated Plasma Protein-A; D005947:Glucose
keywords: Adiposity; Glucose metabolism; IGF-axis; Insulin-like growth factor; Insulin-like growth factor binding protein; Pappalysin-2