P A Nidhina Haridas1, Jarkko Soronen1, Sanja Sädevirta1, Raghavendra Mysore1, Fabiana Quagliarini1, Arja Pasternack1, Jari Metso1, Julia Perttilä1, Marja Leivonen1, Cynthia M Smas1, Pamela Fischer-Posovszky1, Martin Wabitsch1, Christian Ehnholm1, Olli Ritvos1, Matti Jauhiainen1, Vesa M Olkkonen1, Hannele Yki-Järvinen1. 1. Minerva Foundation Institute for Medical Research (P.A.N.H., J.S., S.S., R.M., J.P., V.M.O., H.J.-J.), FI-00290 Helsinki, Finland; Public Health Genomics Unit (J.S., J.M., C.E., M.J.), National Institute for Health and Welfare, Helsinki, FI-00290 Helsinki, Finland; Department of Medicine (S.S.), FI-00014 University of Helsinki, Helsinki, Finland; Department of Internal Medicine (F.Q.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Haartman Institute (A.P., O.R.), FI-00014 University of Helsinki, FI-00029 Helsinki, Finland; Department of Surgery (M.L.), Helsinki University Central Hospital, University of Helsinki, FI-00029 Helsinki, Finland; Department of Biochemistry and Cancer Biology and Center for Diabetes and Endocrine Research (C.M.S.), University of Toledo College of Medicine, Toledo, Ohio 43614; Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine (P.F.-P., M.W.), University of Ulm, D-89075 Ulm Germany.
Abstract
OBJECTIVE: Circulating ANGPTL8 has recently been used as a marker of insulin action. We studied expression and insulin regulation of ANGPTL8 and ANGPTL3 in vivo and in vitro. DESIGN AND METHODS: Expression of ANGPTL8 and ANGPTL3 was studied in 34 paired samples of human liver and adipose tissue. Effects of insulin on 1) plasma concentrations and adipose tissue expression of ANGPTL8 and ANGPTL3 (in vivo 6-h euglycemic hyperinsulinemia; n = 18), and 2) ANGPTL8 and ANGPTL3 gene and protein expression in immortalized human hepatocytes (IHH) and adipocytes were measured. Effect of ANGPTL3 on secretion of ANGPTL8 in cells stably overexpressing ANGPTL3, -8, or both was determined. RESULTS: ANGPTL3 was only expressed in the liver, whereas ANGPTL8 was expressed in both tissues. In vivo hyperinsulinemia significantly decreased both plasma ANGPTL8 and ANGPTL3 at 3 and 6 hours. Insulin increased ANGPTL8 expression in human adipose tissue 14- and 18-fold at 3 and 6 hours and ANGPTL8 was the most insulin-responsive transcript on microarray. Insulin also increased ANPGTL8 in cultured adipocytes and IHH but the protein mainly remained intracellular. In vitro in IHH, insulin decreased ANGPTL3 gene expression and secretion of ANGPTL3 into growth medium. Overexpression of ANGPTL8 in CHO cells did not result in its release into culture medium while abundant secretion occurred in cells co-expressing ANGPTL3 and -8. CONCLUSIONS: Insulin decreases plasma ANGPTL3 by decreasing ANGPTL3 expression in the liver. Insulin markedly increases ANGPTL8 in adipose tissue and the liver but not in plasma. These data show that measurement of plasma ANGPTL3 but not -8 reflects insulin action in target tissues.
OBJECTIVE: Circulating ANGPTL8 has recently been used as a marker of insulin action. We studied expression and insulin regulation of ANGPTL8 and ANGPTL3 in vivo and in vitro. DESIGN AND METHODS: Expression of ANGPTL8 and ANGPTL3 was studied in 34 paired samples of human liver and adipose tissue. Effects of insulin on 1) plasma concentrations and adipose tissue expression of ANGPTL8 and ANGPTL3 (in vivo 6-h euglycemic hyperinsulinemia; n = 18), and 2) ANGPTL8 and ANGPTL3 gene and protein expression in immortalized human hepatocytes (IHH) and adipocytes were measured. Effect of ANGPTL3 on secretion of ANGPTL8 in cells stably overexpressing ANGPTL3, -8, or both was determined. RESULTS:ANGPTL3 was only expressed in the liver, whereas ANGPTL8 was expressed in both tissues. In vivo hyperinsulinemia significantly decreased both plasma ANGPTL8 and ANGPTL3 at 3 and 6 hours. Insulin increased ANGPTL8 expression in human adipose tissue 14- and 18-fold at 3 and 6 hours and ANGPTL8 was the most insulin-responsive transcript on microarray. Insulin also increased ANPGTL8 in cultured adipocytes and IHH but the protein mainly remained intracellular. In vitro in IHH, insulin decreased ANGPTL3 gene expression and secretion of ANGPTL3 into growth medium. Overexpression of ANGPTL8 in CHO cells did not result in its release into culture medium while abundant secretion occurred in cells co-expressing ANGPTL3 and -8. CONCLUSIONS:Insulin decreases plasma ANGPTL3 by decreasing ANGPTL3 expression in the liver. Insulin markedly increases ANGPTL8 in adipose tissue and the liver but not in plasma. These data show that measurement of plasma ANGPTL3 but not -8 reflects insulin action in target tissues.
Authors: Ranganath Muniyappa; Brent S Abel; Asha Asthana; Mary F Walter; Elaine K Cochran; Alan T Remaley; Monica C Skarulis; Phillip Gorden; Rebecca J Brown Journal: J Clin Lipidol Date: 2017-02-24 Impact factor: 4.766
Authors: Soo Ghee Yeoh; Jia Siang Sum; Jing Yi Lai; W Y Haniff W Isa; Theam Soon Lim Journal: J Cardiovasc Transl Res Date: 2021-08-31 Impact factor: 3.216
Authors: Ilenia Minicocci; Anna Tikka; Eleonora Poggiogalle; Jari Metso; Anna Montali; Fabrizio Ceci; Giancarlo Labbadia; Mario Fontana; Alessia Di Costanzo; Marianna Maranghi; Aldo Rosano; Christian Ehnholm; Lorenzo Maria Donini; Matti Jauhiainen; Marcello Arca Journal: J Lipid Res Date: 2016-04-03 Impact factor: 5.922
Authors: Federico Oldoni; Kevin Bass; Julia Kozlitina; Hannah Hudson; Lisa M Shihanian; Viktoria Gusarova; Jonathan C Cohen; Helen H Hobbs Journal: J Clin Endocrinol Metab Date: 2021-05-13 Impact factor: 5.958