Elucidation of the role of FSTL3/Activin axis in the development of obesity-induced diabetes

2014 Fiscal Year Final Research Report

• Project/Area Number: 24249053
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: UEKI Kohjiro 東京大学, 医学部附属病院, 特任教授 (00396714)
• Co-Investigator(Renkei-kenkyūsha): OKAZAKI Yukiko 東京大学, 医学部附属病院, 助教 (30422299) ; SUWANAI Hirotsugu 東京大学, 医学部附属病院, 助教 (60624939) ; SASAKO Takayoshi 東京大学, 医学部附属病院, 特任助教 (20550429) ; KOBAYASI Masatoshi 東京大学, 医学部附属病院, 特任助教 (30396725)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 糖尿病 / 肥満 / アディポカイン

Outline of Final Research Achievements

We have identified FSTL3 as an adipokine whose expression starts increasing at the very early stage of obesity. Adenovirus-mediated gene transfer of FSTL3 in mice resulted in impaired glucose tolerance, while suppression of FSTL3 by an antisense oligonucleotide or a neutralizing antibody improved it in obese diabetic mice. On the other hand, Adenovirus-mediated gene transfer or administration of Activin B, which is known to bind to FSTL3, markedly ameliorated impaired glucose homeostasis in obese diabetic mice. We have found that this beneficial effect of Activin B is mediated through enhancement of insulin secretion, suppression of hepatic gluconeogenesis and improvement of insulin sensitivity. These data suggest that modulation of FSTL3/Activin axis may be a promising therapeutic strategy for the treatment of obesity-induced diabetes.

Free Research Field

糖尿病代謝内科学