Loss of ACE2 exaggerates high-calorie diet-induced insulin resistance by reduction of GLUT4 in mice.
Diabetes
; 62(1): 223-33, 2013 Jan.
Article
in En
| MEDLINE
| ID: mdl-22933108
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin Resistance
/
Peptidyl-Dipeptidase A
/
Glucose Transporter Type 4
Limits:
Animals
Language:
En
Journal:
Diabetes
Year:
2013
Document type:
Article
Affiliation country:
Japan