The clinical use of angiotensin-converting enzyme (ACE) inhibitors has been associated with increased insulin sensitivity. However, the molecular mechanism is unknown. The authors examined the early steps in insulin action, i.e., the phosphorylation status of the insulin receptor and of the pp185 in liver and muscle of obese rats treated acutely with captopril, using immunoblotting with antiphosphotyrosine antibodies. Following treatment with captopril there was an improvement in insulin-induced insulin receptor and pp185 phosphorylation in the liver and muscle of obese rats. This finding contribute to an explanation of the mechanism by which ACE inhibitors appear to improve insulin sensitivity.46259-66