Blazar B R, Whitley C B, Kitabchi A E, Tsai M Y, Santiago J, White N, Stentz F B, Brown D M
Diabetes. 1984 Dec;33(12):1133-7. doi: 10.2337/diab.33.12.1133.
We report on a 26-yr-old patient with an 11-yr history of insulin-dependent diabetes mellitus who exhibited insulin resistance with a requirement of up to 15,000 U of intravenous (i.v.) insulin/day. Attempts to diminish her insulin requirement by administration of sulfated insulin or Trasylol were unsuccessful, with the patient remaining resistant to subcutaneous (s.c.) and i.v. administration of pure pork insulin. Chloroquine phosphate therapy (500 mg twice a day) resulted in a decreased requirement for i.v. insulin (700 U/day as compared with the pretreatment requirement of 8400 U/day). Accelerated insulin degradation in s.c. fat tissue of the patient before treatment with chloroquine was demonstrated. This activity was decreased by 64% during chloroquine therapy. Inhibition of insulin degrading activity (IDA) during chloroquine therapy was associated with reductions in the leukocyte lysosomal enzymes alpha-galactosidase and hexosaminidase-A but not hexosaminidase-B and beta-glucuronidase. This study constitutes the first reported use of chloroquine for treatment of insulin resistance as a result of accelerated insulin degradation, and it provides evidence of the effectiveness of this agent in this rare condition.
我们报告了一名26岁的胰岛素依赖型糖尿病患者，其病史长达11年，表现出胰岛素抵抗，每天需要高达15,000单位的静脉注射胰岛素。通过给予硫酸化胰岛素或抑肽酶来减少其胰岛素需求量的尝试均未成功，该患者对皮下和静脉注射纯猪胰岛素仍有抵抗。磷酸氯喹治疗（每日两次，每次500毫克）使静脉注射胰岛素的需求量减少（与治疗前每天8400单位的需求量相比，降至每天700单位）。在用氯喹治疗前，已证实该患者皮下脂肪组织中胰岛素降解加速。在氯喹治疗期间，这种活性降低了64%。氯喹治疗期间胰岛素降解活性（IDA）的抑制与白细胞溶酶体酶α-半乳糖苷酶和氨基己糖苷酶-A的减少有关，但与氨基己糖苷酶-B和β-葡萄糖醛酸酶无关。本研究是首次报道使用氯喹治疗因胰岛素降解加速导致的胰岛素抵抗，并且提供了该药物在这种罕见病症中有效性的证据。
