Plasma Adiponectin Levels Are Markedly Elevated in Imatinib-Treated Chronic Myeloid Leukemia (CML) Patients: A Mechanism for Improved Insulin Sensitivity in Type 2 Diabetic CML Patients?
Plasma Adiponectin Levels Are Markedly Elevated in Imatinib-Treated Chronic Myeloid Leukemia (CML) Patients: A Mechanism for Improved Insulin Sensitivity in Type 2 Diabetic CML Patients?
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DOI：
10.1210/jc.2010-0086
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发表时间：
2010-08-01
影响因子：
5.8
通讯作者：
Zannettino, Andrew C. W.
中科院分区：
文献类型：
--
作者：
Fitter, Stephen;Vandyke, Kate;Zannettino, Andrew C. W.
内容：伊马替尼改善慢性粒细胞白血病（CML）合并2型糖尿病患者血糖控制的机制尚不清楚。目的：脂联素是胰岛素敏感性的重要调节因子，仅由脂肪细胞分泌。我们以前报道过伊马替尼促进间充质基质细胞向脂肪细胞分化。因此，我们假设伊马替尼治疗将与外周和髓内肥胖和血浆脂联素水平升高的增加，研究设计和方法：脂联素水平在CML患者血浆中，在诊断，然后在伊马替尼甲磺酸盐治疗，使用ELISA测定。采用非变性PAGE和免疫印迹法分析血浆中脂联素多聚体。分别采用组织形态计量学和双能X线吸收法测定髓内脂肪和脂肪组织质量。在CML患者中，伊马替尼治疗6个月后观察到髓内和外周肥胖增加，与治疗前水平相比，治疗3、6、10、12、14、15、16、17、18、19、1结论：伊马替尼治疗的CML患者脂联素水平升高提供了一种可能的机制，改善了一些伊马替尼治疗患者的糖和脂质代谢。（临床内分泌代谢杂志95：3763-3767，2010）
Context: The mechanism(s) by which imatinib improves glycemic control in chronic myeloid leukemia (CML) patients with type 2 diabetes remains unclear.Objective: Adiponectin is an important regulator of insulin sensitivity that is secreted exclusively by adipocytes. We previously reported that imatinib promotes adipocytic differentiation of mesenchymal stromal cells. We therefore hypothesized that imatinib therapy would be associated with an increase in peripheral and intramedullary adiposity and elevated plasma adiponectin levels.Research Design and Methods: Adiponectin levels in CML patient plasma, at diagnosis and then during imatinib mesylate therapy, was measured using an ELISA. Adiponectin multimers in plasma were analyzed using nondenaturing PAGE and immunoblotting. Intramedullary adiposity and adipose tissue mass was determined using histomorphometry and dual-energy X-ray absorptiometry, respectively.Results: In CML patients, an increase in intramedullary and peripheral adiposity was observed after 6 months of imatinib therapy and plasma adiponectin levels, in the form of high-and low-molecular-weight complexes, were elevated 3-fold, compared with pretreatment levels, after 3, 6, and 12 months of therapy.Conclusions: Elevated adiponectin levels in imatinib-treated CML patients provide a possible mechanism for improved glucose and lipid metabolism reported for some imatinib-treated patients. (J Clin Endocrinol Metab 95: 3763-3767, 2010)