Julian K Christians1, Amrit K Bath2, Neilab Amiri2. 1. Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada. Electronic address: jkchrist@sfu.ca. 2. Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
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. DESIGN: 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.
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. DESIGN: 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: Katherine Xu; Paul Rosenstiel; Neal Paragas; Christian Hinze; Xiaobo Gao; Tian Huai Shen; Max Werth; Catherine Forster; Rong Deng; Efrat Bruck; Roger W Boles; Alexandra Tornato; Tejashree Gopal; Madison Jones; Justin Konig; Jacob Stauber; Vivette D'Agati; Hediye Erdjument-Bromage; Subodh Saggi; Gebhard Wagener; Kai M Schmidt-Ott; Nicholas Tatonetti; Paul Tempst; Juan A Oliver; Paolo Guarnieri; Jonathan Barasch Journal: J Am Soc Nephrol Date: 2016-12-27 Impact factor: 10.121
Authors: Mariaelisa Graff; Robert A Scott; Anne E Justice; Kristin L Young; Mary F Feitosa; Llilda Barata; Thomas W Winkler; Audrey Y Chu; Anubha Mahajan; David Hadley; Luting Xue; Tsegaselassie Workalemahu; Nancy L Heard-Costa; Marcel den Hoed; Tarunveer S Ahluwalia; Qibin Qi; Julius S Ngwa; Frida Renström; Lydia Quaye; John D Eicher; James E Hayes; Marilyn Cornelis; Zoltan Kutalik; Elise Lim; Jian'an Luan; Jennifer E Huffman; Weihua Zhang; Wei Zhao; Paula J Griffin; Toomas Haller; Shafqat Ahmad; Pedro M Marques-Vidal; Stephanie Bien; Loic Yengo; Alexander Teumer; Albert Vernon Smith; Meena Kumari; Marie Neergaard Harder; Johanne Marie Justesen; Marcus E Kleber; Mette Hollensted; Kurt Lohman; Natalia V Rivera; John B Whitfield; Jing Hua Zhao; Heather M Stringham; Leo-Pekka Lyytikäinen; Charlotte Huppertz; Gonneke Willemsen; Wouter J Peyrot; Ying Wu; Kati Kristiansson; Ayse Demirkan; Myriam Fornage; Maija Hassinen; Lawrence F Bielak; Gemma Cadby; Toshiko Tanaka; Reedik Mägi; Peter J van der Most; Anne U Jackson; Jennifer L Bragg-Gresham; Veronique Vitart; Jonathan Marten; Pau Navarro; Claire Bellis; Dorota Pasko; Åsa Johansson; Søren Snitker; Yu-Ching Cheng; Joel Eriksson; Unhee Lim; Mette Aadahl; Linda S Adair; Najaf Amin; Beverley Balkau; Juha Auvinen; John Beilby; Richard N Bergman; Sven Bergmann; Alain G Bertoni; John Blangero; Amélie Bonnefond; Lori L Bonnycastle; Judith B Borja; Søren Brage; Fabio Busonero; Steve Buyske; Harry Campbell; Peter S Chines; Francis S Collins; Tanguy Corre; George Davey Smith; Graciela E Delgado; Nicole Dueker; Marcus Dörr; Tapani Ebeling; Gudny Eiriksdottir; Tõnu Esko; Jessica D Faul; Mao Fu; Kristine Færch; Christian Gieger; Sven Gläser; Jian Gong; Penny Gordon-Larsen; Harald Grallert; Tanja B Grammer; Niels Grarup; Gerard van Grootheest; Kennet Harald; Nicholas D Hastie; Aki S Havulinna; Dena Hernandez; Lucia Hindorff; Lynne J Hocking; Oddgeir L Holmens; Christina Holzapfel; Jouke Jan Hottenga; Jie Huang; Tao Huang; Jennie Hui; Cornelia Huth; Nina Hutri-Kähönen; Alan L James; John-Olov Jansson; Min A Jhun; Markus Juonala; Leena Kinnunen; Heikki A Koistinen; Ivana Kolcic; Pirjo Komulainen; Johanna Kuusisto; Kirsti Kvaløy; Mika Kähönen; Timo A Lakka; Lenore J Launer; Benjamin Lehne; Cecilia M Lindgren; Mattias Lorentzon; Robert Luben; Michel Marre; Yuri Milaneschi; Keri L Monda; Grant W Montgomery; Marleen H M De Moor; Antonella Mulas; Martina Müller-Nurasyid; A W Musk; Reija Männikkö; Satu Männistö; Narisu Narisu; Matthias Nauck; Jennifer A Nettleton; Ilja M Nolte; Albertine J Oldehinkel; Matthias Olden; Ken K Ong; Sandosh Padmanabhan; Lavinia Paternoster; Jeremiah Perez; Markus Perola; Annette Peters; Ulrike Peters; Patricia A Peyser; Inga Prokopenko; Hannu Puolijoki; Olli T Raitakari; Tuomo Rankinen; Laura J Rasmussen-Torvik; Rajesh Rawal; Paul M Ridker; Lynda M Rose; Igor Rudan; Cinzia Sarti; Mark A Sarzynski; Kai Savonen; William R Scott; Serena Sanna; Alan R Shuldiner; Steve Sidney; Günther Silbernagel; Blair H Smith; Jennifer A Smith; Harold Snieder; Alena Stančáková; Barbara Sternfeld; Amy J Swift; Tuija Tammelin; Sian-Tsung Tan; Barbara Thorand; Dorothée Thuillier; Liesbeth Vandenput; Henrik Vestergaard; Jana V van Vliet-Ostaptchouk; Marie-Claude Vohl; Uwe Völker; Gérard Waeber; Mark Walker; Sarah Wild; Andrew Wong; Alan F Wright; M Carola Zillikens; Niha Zubair; Christopher A Haiman; Loic Lemarchand; Ulf Gyllensten; Claes Ohlsson; Albert Hofman; Fernando Rivadeneira; André G Uitterlinden; Louis Pérusse; James F Wilson; Caroline Hayward; Ozren Polasek; Francesco Cucca; Kristian Hveem; Catharina A Hartman; Anke Tönjes; Stefania Bandinelli; Lyle J Palmer; Sharon L R Kardia; Rainer Rauramaa; Thorkild I A Sørensen; Jaakko Tuomilehto; Veikko Salomaa; Brenda W J H Penninx; Eco J C de Geus; Dorret I Boomsma; Terho Lehtimäki; Massimo Mangino; Markku Laakso; Claude Bouchard; Nicholas G Martin; Diana Kuh; Yongmei Liu; Allan Linneberg; Winfried März; Konstantin Strauch; Mika Kivimäki; Tamara B Harris; Vilmundur Gudnason; Henry Völzke; Lu Qi; Marjo-Riitta Järvelin; John C Chambers; Jaspal S Kooner; Philippe Froguel; Charles Kooperberg; Peter Vollenweider; Göran Hallmans; Torben Hansen; Oluf Pedersen; Andres Metspalu; Nicholas J Wareham; Claudia Langenberg; David R Weir; David J Porteous; Eric Boerwinkle; Daniel I Chasman; Gonçalo R Abecasis; Inês Barroso; Mark I McCarthy; Timothy M Frayling; Jeffrey R O'Connell; Cornelia M van Duijn; Michael Boehnke; Iris M Heid; Karen L Mohlke; David P Strachan; Caroline S Fox; Ching-Ti Liu; Joel N Hirschhorn; Robert J Klein; Andrew D Johnson; Ingrid B Borecki; Paul W Franks; Kari E North; L Adrienne Cupples; Ruth J F Loos; Tuomas O Kilpeläinen Journal: PLoS Genet Date: 2017-04-27 Impact factor: 5.917