Captopril normalizes insulin signaling and insulin-regulated substrate
metabolism in obese (ob/ob) mouse hearts
Authors Tabbi-Anneni I, Buchanan J, Cooksey RC, Abel ED.
Submitted By E. Dale Abel on 12/19/2008
Status Published
Journal Endocrinology
Year 2008
Date Published 8/1/2008
Volume : Pages 149 : 4043 - 4050
PubMed Reference 18450963
Abstract 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.

Investigators with authorship
E. Dale AbelUniversity of Iowa


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