Ken Sugimoto
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of General Geriatric Medicine,
   Position   Professor
Article types 原著
Language English
Peer review Peer reviewed
Title Loss of ACE2 exaggerates high-calorie diet-induced insulin resistance by reduction of GLUT4 in mice.
Journal Formal name：Diabetes
Abbreviation：Diabetes
ISSN code：1939327X/00121797
Domestic / ForeginForegin
Volume, Issue, Page 62(1),pp.223-233
Author and coauthor Takeda Masao, Yamamoto Koichi, Takemura Yukihiro, Takeshita Hikari, Hongyo Kazuhiro, Kawai Tatsuo, Hanasaki-Yamamoto Hiroko, Oguro Ryosuke, Takami Yoichi, Tatara Yuji, Takeya Yasushi, Sugimoto Ken, Kamide Kei, Ohishi Mitsuru, Rakugi Hiromi
Publication date 2013/01
Summary ACE type 2 (ACE2) functions as a negative regulator of the renin-angiotensin system by cleaving angiotensin II (AII) into angiotensin 1-7 (A1-7). This study assessed the role of endogenous ACE2 in maintaining insulin sensitivity. Twelve-week-old male ACE2 knockout (ACE2KO) mice had normal insulin sensitivities when fed a standard diet. AII infusion or a high-fat, high-sucrose (HFHS) diet impaired glucose tolerance and insulin sensitivity more severely in ACE2KO mice than in their wild-type (WT) littermates. The strain difference in glucose tolerance was not eliminated by an AII receptor type 1 (AT1) blocker but was eradicated by A1-7 or an AT1 blocker combined with the A1-7 inhibitor (A779). The expression of GLUT4 and a transcriptional factor, myocyte enhancer factor (MEF) 2A, was dramatically reduced in the skeletal muscles of the standard diet-fed ACE2KO mice. The expression of GLUT4 and MEF2A was increased by A1-7 in ACE2KO mice and decreased by A779 in WT mice. A1-7 enhanced upregulation of MEF2A and GLUT4 during differentiation of myoblast cells. In conclusion, ACE2 protects against high-calorie diet-induced insulin resistance in mice. This mechanism may involve the transcriptional regulation of GLUT4 via an A1-7-dependent pathway.
DOI 10.2337/db12-0177
PMID 22933108