Evidence for a role of glucocorticoids in the development of insulin resistance after ischaemic limb injury in the rat.
Bilateral hind-limb ischaemia in the rat is known to cause insulin resistance, as shown by a sustained rise in plasma glucose concentration with a decreased metabolic clearance rate but no fall in plasma insulin. However, when the concomitant rise in the plasma concentration of corticosterone was diminished by an inhibitor of its biosynthesis, trilostane (WIN 24 540), the hyperglycaemia became transient. The mechanism of this effect has now been studied by measuring the rate of disappearance of [5-3H,U-14C]glucose and the concentration of insulin in plasma. Trilostane did not alter the rate of glucose production or the 3H : 14C ratio (an index of recycling through gluconeogenic precursors). It did , however, raise the metabolic clearance rate while lowering the plasma insulin concentration, i.e. peripheral sensitivity and/or responsiveness to insulin was increased. Insulin resistance was restored by giving corticosterone together with trilostane. Thus an increased concentration of corticosterone in the plasma was necessary for the full development of insulin resistance following ischaemic limb injury. It was, however, probably not the only factor since a similar dose of corticosterone did not lead to hyperglycaemia in uninjured rats.
D000302:Adrenal Cortex / Q000502:physiology*; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D013196:Dihydrotestosterone / Q000031:analogs & derivatives*; D006614:Hindlimb / Q000098:blood supply; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007511:Ischemia / Q000097:blood*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D051381:Rats
D000732:Androstanols; D001786:Blood Glucose; D007328:Insulin; D009570:Nitriles; D013196:Dihydrotestosterone; C009954:trilostane; D003345:Corticosterone