Molecular Mechanism of Moderate Insulin Resistance in Adiponectin-Knockout Mice

• YANO Wataru

  Department of Diabetes and Metabolic Disease, Graduate School of Medicine, University of Tokyo

• KUBOTA Naoto

  Department of Diabetes and Metabolic Disease, Graduate School of Medicine, University of Tokyo Translational Systems Biology and Medicine Initiative, University of Tokyo Division of Applied Nutrition, National Institute of Health and Nutrition

• ITOH Shinsuke

  Department of Diabetes and Metabolic Disease, Graduate School of Medicine, University of Tokyo

• KUBOTA Tetsuya

  Department of Diabetes and Metabolic Disease, Graduate School of Medicine, University of Tokyo Division of Applied Nutrition, National Institute of Health and Nutrition Division of Cardiovascular Medicine, Toho University, Ohashi Hospital

• AWAZAWA Motoharu

  Department of Diabetes and Metabolic Disease, Graduate School of Medicine, University of Tokyo

• MOROI Masao

  Division of Cardiovascular Medicine, Toho University, Ohashi Hospital

• SUGI Kaoru

  Division of Cardiovascular Medicine, Toho University, Ohashi Hospital

• TAKAMOTO Iseki

  Department of Diabetes and Metabolic Disease, Graduate School of Medicine, University of Tokyo Translational Systems Biology and Medicine Initiative, University of Tokyo Division of Applied Nutrition, National Institute of Health and Nutrition

• OGATA Hitomi

  Graduate School of Comprehensive Human Sciences, University of Tsukuba

• TOKUYAMA Kumpei

  Graduate School of Comprehensive Human Sciences, University of Tsukuba

• NODA Tetsuo

  Department of Cell Biology, Japanese Foundation for Cancer Research-Cancer Institute

• TERAUCHI Yasuo

  Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine

• UEKI Kohjiro

  Department of Diabetes and Metabolic Disease, Graduate School of Medicine, University of Tokyo

• KADOWAKI Takashi

  Department of Diabetes and Metabolic Disease, Graduate School of Medicine, University of Tokyo Translational Systems Biology and Medicine Initiative, University of Tokyo Division of Applied Nutrition, National Institute of Health and Nutrition

Abstract

Adiponectin has been proposed to act as an antidiabetic adipokine, suppressing gluconeogenesis and stimulating fatty acid oxidation in the liver and skeletal muscle. Although adiponectin-knockout (adipo(-/-)) mice are known to exhibit insulin resistance, the degrees of insulin resistance and glucose intolerance are unexpectedly only moderate. In this study, the adipo(-/-) mice showed hepatic, but not muscle, insulin resistance. insulin-stimulated phosphorylation of IRS-1 and IRS-2 was impaired, the IRS-2 protein level was decreased, and insulin-stimulated phosphorylation of Akt was decreased in the liver of the adipo(-/-) mice. However, the triglyceride content in the liver was not increased in these mice, despite the decrease in the PPARalpha expression involved in lipid combustion, since the expressions of lipogenic genes such as SREBP-1 and SCD-1 were decreased in association with the increased leptin sensitivity. Consistent with this, the down-regulation SREBP-1 and SCD-1 observed in the adipo(-/-) mice was no longer observed, and the hepatic triglyceride content was significantly increased in the adiponectin leptin double-knockout (adipo(-/-)ob/ob) mice. On the other hand, the triglyceride content in the skeletal muscle was significantly decreased in the adipo(-/-) mice, probably due to up-regulated AMPK activity associated with the increased leptin sensitivity. In fact, these phenotypes in the skeletal muscle of these mice were no longer observed in the adipo(-/-)ob/ob mice. In conclusion, adipo(-/-) mice showed impaired insulin signaling in the liver to cause hepatic insulin resistance, however, no increase in the triglyceride content was observed in either the liver or the skeletal muscle, presumably on account of the increased leptin sensitivity.<br>

Journal

• Endocrine Journal

  Endocrine Journal 55 (3), 515-522, 2008

  The Japan Endocrine Society

Keywords

• Adiponectin
• Insulin resistance
• Adiponectin-knockout mice
• Euglycemic-hyperinsulinemic clamp

Details

• CRID: 1390001206299463168
• NII Article ID: 10021266439
• NII Book ID: AA10901436
• DOI: 10.1507/endocrj.k08e-093
• ISSN: 13484540
• ISSN: 09188959
• Web Site: http://www.jstage.jst.go.jp/article/endocrj/55/3/55_K08E-093/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2008285031
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed