MODE OF ACTION OF CHLOROQUINE IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS
MODE OF ACTION OF CHLOROQUINE IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS
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DOI：
10.1152/ajpendo.1991.260.6.e897
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发表时间：
1991-06-01
影响因子：
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通讯作者：
JONES, RH
中科院分区：
文献类型：
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作者：
POWRIE, JK;SMITH, GD;JONES, RH
临床研究表明，氯喹和羟氯喹可改善胰岛素抵抗型糖尿病患者的糖代谢。 作用机制尚未确定。 我们进行了一项随机、双盲、安慰剂对照试验，在20例饮食控制的非胰岛素依赖型糖尿病患者中口服磷酸氯喹250 mg，每日4次，为期3天。 在用氯喹或安慰剂治疗之前和之后，通过在高胰岛素正葡萄糖钳夹期间输注稳定的同位素标记的D-葡萄糖（[6，6-H-2（2）]葡萄糖）来评估葡萄糖出现率（R（a））和消失率（R（d））。 氯喹使空腹血糖从199.8 +/- 8.6 mg/dl显著改善至165.6 +/- 7.6 mg/dl（P < 0.01）。 由于R（d）增加（2，348.0 - 2，618.9 mg.kg-1.330 min-1，P <0.01）而R（a）无变化，维持正常血糖所需的总外源性葡萄糖输注量显著增加（1，792.6 - 2，040.1 mg.kg-1.330 min-1，P <0.05）。 在血浆胰岛素水平为150-200 mU/l时，胰岛素的代谢清除率从14.4 +/- 1.3降至11.0 +/- 0.6 ml.kg-1.min-1（P < 0.01），但在2，000 - 3，000 mU/l时未发生这种情况。 此外，在低剂量和高剂量胰岛素输注期间，氯喹使空腹C肽分泌增加17%，并使C肽的反馈抑制分别减少9.1%和10.6%。
Clinical studies have demonstrated that chloroquine and hydroxychloroquine improve glucose metabolism in patients with insulin-resistant diabetes mellitus. The mechanism of action has not been determined. We undertook a randomized double-blind placebo-controlled trial of 3 days of oral chloroquine phosphate, 250 mg four times daily, in 20 patients with non-insulin-dependent diabetes mellitus controlled by diet. Rates of glucose appearance (R(a)) and disapperance (R(d)) were evaluated by infusion of stable isotopically labeled D-glucose ([6,6-H-2(2)]glucose) during hyperinsulinemic euglycemic clamps before and after treatment with chloroquine or placebo. Chloroquine significantly improved fasting plasma glucose from 199.8 +/- 8.6 to 165.6 +/- 7.6 mg/dl (P < 0.01). Total exogenous glucose infusion required to maintain euglycemia significantly increased (1,792.6-2,040.1 mg.kg-1.330 min-1, P < 0.05) due to an increase in R(d) (2,348.0-2,618.9 mg.kg-1.330 min-1, P < 0.01) without change in R(a). Metabolic clearance rate of insulin decreased by 39% from 14.4 +/- 1.3 to 11.0 +/- 0.6 ml.kg-1.min-1 (P < 0.01) at plasma insulin levels of 150-200 mU/l but not at levels of 2,000-3,000 mU/l. In addition, chloroquine increased fasting C-peptide secretion by 17% and reduced feedback inhibition of C-peptide by 9.1 and 10.6% during low- and high-dose insulin infusions, respectively.