Diabetologia

, Volume 44, Issue 5, pp 555–566

The effects of brain-derived neurotrophic factor on insulin signal transduction in the liver of diabetic mice

  • A. Tsuchida
  • T. Nakagawa
  • Y. Itakura
  • J. Ichihara
  • W. Ogawa
  • M. Kasuga
  • M. Taiji
  • H. Noguchi
Article

DOI: 10.1007/s001250051661

Cite this article as:
Tsuchida, A., Nakagawa, T., Itakura, Y. et al. Diabetologia (2001) 44: 555. doi:10.1007/s001250051661

Abstract

Aim/hypothesis. We previously reported that repeated subcutaneous or intracerebroventricular injection of brain-derived neurotrophic factor (BDNF) reduces blood glucose concentrations in obese diabetic C57BL/KsJ-db/db mice. In this study, we assessed the effects of BDNF on insulin action in peripheral tissues of diabetic mice. Methods. First, brain-derived neurotrophic factor (20 mg/kg) was subcutaneously given to male db/db mice for 14 days and then the insulin-stimulated tyrosine phosphorylation of insulin receptors and insulin-stimulated phosphatidylinositol (PI) 3-kinase activity in peripheral tissues was assessed. Second, we examined the effects of a single subcutaneous or intracerebroventricular brain-derived neurotrophic factor injection on insulin responsiveness in liver and skeletal muscle of streptozotocin (STZ)-induced diabetic mice. Third, the effects of brain-derived neurothrophic factor on insulin action were also examined in cultured cells. Results. Repeated injection of BDNF to db/db mice for 14 days enhanced insulin-stimulated tyrosine phosphorylation of insulin receptors in liver and insulin-stimulated PI 3-kinase activity in liver, skeletal muscle and interscapular brown adipose tissue. We then examined the rapid effect of BDNF on insulin signalling in vivo. A single subcutaneous or intracerebroventricular injection of BDNF rapidly increased insulin-stimulated tyrosine phosphorylation of insulin receptors and PI 3-kinase activity in liver of STZ-mice. No direct effect of brain-derived neurothrophic factor was observed on insulin signalling in primary cultured hepatocytes, L6 muscle cells or 3T3-L1 adipocytes. Brain-derived neurothrophic factor did not affect either glucose uptake or gluconeogenesis in these cells. Conclusion/interpretation. These data indicate that brain-derived neurothrophic factor rapidly enhances insulin signal transduction in liver and shows hypoglycaemic action in diabetic mice. [Diabetologia (2001) 44: 555–566]

Keywords Neurotrophic factorinsulin responsivenessglucose uptakediabetic miceinsulin signalling.
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Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • A. Tsuchida
    • 1
  • T. Nakagawa
    • 1
  • Y. Itakura
    • 1
  • J. Ichihara
    • 1
  • W. Ogawa
    • 2
  • M. Kasuga
    • 2
  • M. Taiji
    • 1
  • H. Noguchi
    • 1
  1. 1.Sumitomo Pharmaceuticals, Osaka, JapanJP
  2. 2.The Second Department of Internal Medicine, Kobe University School of Medicine, Kobe, JapanJP