Endocrinology 2008,
PMID: 18450963
Tabbi-Anneni, Imene; Buchanan, Jonathan; Cooksey, Robert C; Abel, E Dale
The goal of this study was to determine whether inhibiting the renin-angiotensin system would restore insulin signaling and normalize substrate use in hearts from obese ob/ob mice. Mice were treated for 4 wk with Captopril (4 mg/kg x d). Circulating levels of free fatty acids, triglycerides, and insulin were measured and glucose tolerance tests performed. Rates of palmitate oxidation and glycolysis, oxygen consumption, and cardiac power were determined in isolated working hearts in the presence and absence of insulin, along with levels of phosphorylation of Akt and AMP-activated protein kinase (AMPK). Captopril treatment did not correct the hyperinsulinemia or impaired glucose tolerance in ob/ob mice. Rates of fatty acid oxidation were increased and glycolysis decreased in ob/ob hearts, and insulin did not modulate substrate use in hearts of ob/ob mice and did not increase Akt phosphorylation. Captopril restored the ability of insulin to regulate fatty acid oxidation and glycolysis in hearts of ob/ob mice, possibly by increasing Akt phosphorylation. Moreover, AMPK phosphorylation, which was increased in hearts of ob/ob mice, was normalized by Captopril treatment, suggesting that in addition to restoring insulin sensitivity, Captopril treatment improved myocardial energetics. Thus, angiotensin-converting enzyme inhibitors restore the responsiveness of ob/ob mouse hearts to insulin and normalizes AMPK activity independently of effects on systemic metabolic homeostasis.
Diseases/Pathways annotated by Medline MESH: Body Weight, Cardiovascular Diseases, Insulin Resistance, Obesity
Document information provided by NCBI PubMed
Text Mining Data
Akt → insulin: "
Rates of fatty acid oxidation were increased and glycolysis decreased in ob/ob hearts, and
insulin did not modulate substrate use in hearts of ob/ob mice and did not
increase Akt phosphorylation
"
Manually curated Databases
No curated data.