AIMS/HYPOTHESIS: The insulin receptor (INSR) has two protein isoforms based on alternative splicing of exon 11. INSR-A promotes cell growth whereas INSR-B predominantly regulates glucose homeostasis. In this study we investigated whether weight loss regulates INSR alternative splicing and the expression of splicing factors in adipose tissue. METHODS: To determine the relative ratio of the INSR splice variants, we implemented the PCR-capillary electrophoresis method with adipose tissue samples from two weight-loss-intervention studies, the Kuopio Obesity Surgery study (KOBS, n = 108) and a very low calorie diet (VLCD) intervention (n = 32), and from the population-based Metabolic Syndrome in Men study (METSIM, n = 49). RESULTS: Expression of INSR-B mRNA variant increased in response to weight loss induced by both bariatric surgery (p = 1 × 10(-5)) and the VLCD (p = 1 × 10(-4)). The adipose tissue expression of INSR-B correlated negatively with fasting insulin levels in the pooled data of the three studies (p = 3 × 10(-22)). Finally, expression of several splicing factors correlated negatively with the expression of the INSR-B variant. The strongest correlation was with HNRNPA1 (p = 1 × 10(-5)), a known regulator of INSR exon 11 splicing. CONCLUSIONS/ INTERPRETATION: INSR splicing is regulated by weight loss and associates with insulin levels. The effect of weight loss on INSR splicing could be mediated by changes in the expression of splicing factors.
AIMS/HYPOTHESIS: The insulin receptor (INSR) has two protein isoforms based on alternative splicing of exon 11. INSR-A promotes cell growth whereas INSR-B predominantly regulates glucose homeostasis. In this study we investigated whether weight loss regulates INSR alternative splicing and the expression of splicing factors in adipose tissue. METHODS: To determine the relative ratio of the INSR splice variants, we implemented the PCR-capillary electrophoresis method with adipose tissue samples from two weight-loss-intervention studies, the Kuopio Obesity Surgery study (KOBS, n = 108) and a very low calorie diet (VLCD) intervention (n = 32), and from the population-based Metabolic Syndrome in Men study (METSIM, n = 49). RESULTS: Expression of INSR-B mRNA variant increased in response to weight loss induced by both bariatric surgery (p = 1 × 10(-5)) and the VLCD (p = 1 × 10(-4)). The adipose tissue expression of INSR-B correlated negatively with fasting insulin levels in the pooled data of the three studies (p = 3 × 10(-22)). Finally, expression of several splicing factors correlated negatively with the expression of the INSR-B variant. The strongest correlation was with HNRNPA1 (p = 1 × 10(-5)), a known regulator of INSR exon 11 splicing. CONCLUSIONS/ INTERPRETATION:INSR splicing is regulated by weight loss and associates with insulin levels. The effect of weight loss on INSR splicing could be mediated by changes in the expression of splicing factors.
Authors: Kun Jiang; Niketa A Patel; James E Watson; Hercules Apostolatos; Eden Kleiman; Olivia Hanson; Masatoshi Hagiwara; Denise R Cooper Journal: Endocrinology Date: 2008-12-30 Impact factor: 4.736
Authors: Jussi Pihlajamäki; Carles Lerin; Paula Itkonen; Tanner Boes; Thomas Floss; Joshua Schroeder; Farrell Dearie; Sarah Crunkhorn; Furkan Burak; Josep C Jimenez-Chillaron; Tiina Kuulasmaa; Pekka Miettinen; Peter J Park; Imad Nasser; Zhenwen Zhao; Zhaiyi Zhang; Yan Xu; Wolfgang Wurst; Hongmei Ren; Andrew J Morris; Stefan Stamm; Allison B Goldfine; Markku Laakso; Mary Elizabeth Patti Journal: Cell Metab Date: 2011-08-03 Impact factor: 27.287
Authors: G Sesti; M A Marini; A N Tullio; A Montemurro; P Borboni; A Fusco; D Accili; R Lauro Journal: Biochem Biophys Res Commun Date: 1991-12-31 Impact factor: 3.575
Authors: Z Huang; N L Bodkin; H K Ortmeyer; M E Zenilman; N J Webster; B C Hansen; A R Shuldiner Journal: J Clin Endocrinol Metab Date: 1996-04 Impact factor: 5.958
Authors: Indrani Talukdar; Supriya Sen; Rodolfo Urbano; James Thompson; John R Yates; Nicholas J G Webster Journal: PLoS One Date: 2011-11-23 Impact factor: 3.240
Authors: Dorota Kaminska; Tiina Kuulasmaa; Sari Venesmaa; Pirjo Käkelä; Maija Vaittinen; Leena Pulkkinen; Matti Pääkkönen; Helena Gylling; Markku Laakso; Jussi Pihlajamäki Journal: Diabetes Date: 2012-10-18 Impact factor: 9.461
Authors: Mercedes Del Río-Moreno; Emilia Alors-Pérez; Sandra González-Rubio; Gustavo Ferrín; Oscar Reyes; Manuel Rodríguez-Perálvarez; Marina E Sánchez-Frías; Rafael Sánchez-Sánchez; Sebastián Ventura; José López-Miranda; Rhonda D Kineman; Manuel de la Mata; Justo P Castaño; Manuel D Gahete; Raúl M Luque Journal: J Clin Endocrinol Metab Date: 2019-08-01 Impact factor: 5.958
Authors: Jessica Latorre; Angeles Aroca; José Manuel Fernández-Real; Luis C Romero; José María Moreno-Navarrete Journal: Antioxidants (Basel) Date: 2022-05-31
Authors: Sarah M Brotman; Chelsea K Raulerson; Swarooparani Vadlamudi; Kevin W Currin; Qiujin Shen; Victoria A Parsons; Apoorva K Iyengar; Tamara S Roman; Terrence S Furey; Johanna Kuusisto; Francis S Collins; Michael Boehnke; Markku Laakso; Päivi Pajukanta; Karen L Mohlke Journal: Am J Hum Genet Date: 2022-01-06 Impact factor: 11.043
Authors: Antonino Belfiore; Roberta Malaguarnera; Veronica Vella; Michael C Lawrence; Laura Sciacca; Francesco Frasca; Andrea Morrione; Riccardo Vigneri Journal: Endocr Rev Date: 2017-10-01 Impact factor: 19.871
Authors: Jussi Pihlajamäki; Charlotte Ling; Sonia García-Calzón; Alexander Perfilyev; Ville Männistö; Vanessa D de Mello; Emma Nilsson Journal: Clin Epigenetics Date: 2017-09-21 Impact factor: 6.551