Barton R N, Passingham B J
J Endocrinol. 1980 Aug;86(2):363-70. doi: 10.1677/joe.0.0860363.
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.
已知大鼠双侧后肢缺血会导致胰岛素抵抗，表现为血浆葡萄糖浓度持续升高，代谢清除率降低，但血浆胰岛素水平无下降。然而，当通过其生物合成抑制剂曲洛司坦（WIN 24 540）降低血浆皮质酮浓度的同时升高时，高血糖症变得短暂。现在通过测量[5-³H，U-¹⁴C]葡萄糖的消失率和血浆胰岛素浓度来研究这种作用的机制。曲洛司坦并未改变葡萄糖生成速率或³H：¹⁴C比值（通过糖异生前体循环的指标）。然而，它确实提高了代谢清除率，同时降低了血浆胰岛素浓度，即外周对胰岛素的敏感性和/或反应性增加。给予皮质酮和曲洛司坦一起可恢复胰岛素抵抗。因此，血浆中皮质酮浓度升高对于缺血性肢体损伤后胰岛素抵抗的充分发展是必要的。然而，这可能不是唯一因素，因为相同剂量的皮质酮在未受伤的大鼠中并未导致高血糖症。
