EFFEKTE EINER AKUTGABE VON TRANDOLAPRIL AUF DIE INSULINSTIMULIERTE GLUKOSEAUFNAHME IM ISOLIERTEN SKELETTMUSKEL DER FA/FA ZUCKER-RATTE

Antihypertensive agents have various effects on glucose metabolism; beta-blockers and thiazides were shown to reduce insulin sensitivity, calcium channel blockers seem to be inert, and α₁-blockers and ACE-inhibitors (AI) tend to improve insulin stimulated glucose uptake after acute and chronic administration. It is, however, not known whether this improvement is caused by an increase in (muscular) blood flow - as both agents cause vasodilation - or whether there is a more specific effect on glucose uptake. We therefore choose a model of isolated muscle to minimize the influence of blood flow; we used an animal model of insulin resistance - the obese Zucker (fa/fa) rat - to test whether acute (3 h) oral administration of the AI trandolapril (without SU-groups) has a direct effect on insulin-stimulated glucose transport activity in skeletal muscle. In vitro glucose transport activity in the epitrochlearis muscle was assessed by 2-deoxyglucose uptake in the absence or presence of insulin (2 mU/ml). Insulin-stimulated 2-deoxyglucose uptake was only ~ 50% as great in muscles from obese animals compared to lean (Fa/-) controls (p < 0.05), but was significantly (p < 0.05) improved by acute (+33%, p < 0.05) treatment with trandolapril. We conclude that the isolated epitrochlearis muscle from the obese Zucker rat is a suitable model for studying insulin resistance in skeletal muscle; that trandolapril significantly improves insulin-stimulated glucose transport activity in skeletal muscle in the obese Zucker rat after acute administration and that SH groups do not seem to play any role. Our data therefore support the hypothesis that the ACE inhibitors as a group can improve glucose disposal via a direct effect on the skeletal muscle glucose transport system.