| First Author | Bernardi S | Year | 2015 |
| Journal | Metabolism | Volume | 64 |
| Issue | 3 | Pages | 406-15 |
| PubMed ID | 25484288 | Mgi Jnum | J:286450 |
| Mgi Id | MGI:6403561 | Doi | 10.1016/j.metabol.2014.11.004 |
| Citation | Bernardi S, et al. (2015) ACE2 deficiency shifts energy metabolism towards glucose utilization. Metabolism 64(3):406-15 |
| abstractText | BACKGROUND: This study aimed at investigating the effects of genetic angiotensin-converting enzyme (ACE) 2 deficiency on glucose homeostasis in the pancreas and skeletal muscle and their reversibility following ACE inhibition. PROCEDURES: ACE2-knockout and C57bl6J mice were placed on a standard diet (SD) or a high-fat diet (HFD) for 12 weeks. An additional group of ACE2-knockout mice was fed a SD and treated with the ACE inhibitor, perindopril (2 mg kg(-1)day(-1)). Glucose and insulin tolerance tests, indirect calorimetry measurements and EchoMRI were performed. Non-esterfied 'free' fatty acid oxidation rate in skeletal muscle was calculated by measuring the palmitate oxidation rate. beta-cell mass was determined by immunostaining. Insulin, collectrin, glucose transporter protein, and peroxisome proliferator-activated receptor-gamma expression were analysed by RT-PCR. Markers of mithocondrial biogenesis/content were also evaluated. MAIN FINDINGS: ACE2-knockout mice showed a beta-cell defect associated with low insulin and collectrin levels and reduced compensatory hypertrophy in response to a HFD, which were not reversed by perindopril. On the other hand, ACE2 deficiency shifted energy metabolism towards glucose utilization, as it increased the respiratory exchange ratio, reduced palmitate oxidation and PCG-1alpha expression in the skeletal muscle, where it up-regulated glucose transport proteins. Treatment of ACE2-knockout mice with perindopril reversed the skeletal muscle changes, suggesting that these were dependent on Angiotensin II (Ang II). PRINCIPAL CONCLUSIONS: ACE2-knockout mice display a beta-cell defect, which does not seem to be dependent on Ang II but may reflect the collectrin-like action of ACE2. This defect seemed to be compensated by the fact that ACE2-knockout mice shifted their energy consumption towards glucose utilisation via Ang II. |
