Tappy L, Randin D, Vollenweider P, Vollenweider L, Paquot N, Scherrer U, Schneiter P, Nicod P, Jéquier E
Institute of Physiology, University of Lausanne, Switzerland.
J Clin Endocrinol Metab. 1994 Oct;79(4):1063-9. doi: 10.1210/jcem.79.4.7962275.
Insulin resistance may result from decreased muscle blood flow, impaired cellular glucose transport, or intracellular deficits of glucose metabolism. The mechanisms responsible for dexamethasone-induced insulin resistance were investigated in healthy human subjects. During a 2-h hyperinsulinemic clamp, dexamethasone decreased glucose uptake, oxidation, and nonoxidative glucose disposal during the first hour. During the second hour, glucose uptake was normalized by means of hyperglycemia; glucose oxidation, however, remained suppressed by dexamethasone. Dexamethasone also abolished the insulin-mediated increase in calf blood flow. When acipimox was administered during the clamps to correct glucocorticoid-induced inhibition of glucose oxidation, dexamethasone decreased whole body glucose uptake and nonoxidative glucose disposal in the same proportion as when no acipimox was administered. However, glucose oxidation and insulin-mediated calf blood flow were normalized after acipimox. During the second hour, exogenous glucose infusion was matched to that used in the control clamp and normalized whole body glucose uptake. However, hyperglycemia developed, indicating insulin resistance. It is concluded that dexamethasone 1) decreases glucose oxidation independently of glucose transport; this inhibition is reversed by acipimox; and 2) decreases whole body glucose uptake independently of increased lipolysis, decreased glucose oxidation, or an altered muscle blood flow.
胰岛素抵抗可能源于肌肉血流量减少、细胞葡萄糖转运受损或葡萄糖代谢的细胞内缺陷。在健康人体受试者中研究了地塞米松诱导胰岛素抵抗的机制。在2小时的高胰岛素钳夹期间，地塞米松在第一个小时内降低了葡萄糖摄取、氧化和非氧化葡萄糖处置。在第二个小时，通过高血糖使葡萄糖摄取恢复正常；然而，葡萄糖氧化仍被地塞米松抑制。地塞米松还消除了胰岛素介导的小腿血流量增加。当在钳夹期间给予阿西莫司以纠正糖皮质激素诱导的葡萄糖氧化抑制时，地塞米松降低全身葡萄糖摄取和非氧化葡萄糖处置的比例与未给予阿西莫司时相同。然而，阿西莫司治疗后葡萄糖氧化和胰岛素介导的小腿血流量恢复正常。在第二个小时，外源性葡萄糖输注量与对照钳夹中使用的量相匹配，并使全身葡萄糖摄取恢复正常。然而，出现了高血糖，表明存在胰岛素抵抗。结论是地塞米松1）独立于葡萄糖转运降低葡萄糖氧化；这种抑制可被阿西莫司逆转；2）独立于脂解增加、葡萄糖氧化降低或肌肉血流量改变降低全身葡萄糖摄取。
