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|Title:||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?|
|Citation:||Journal of Clinical Endocrinology and Metabolism, 2010; 95(8):3763-3767|
|Stephen Fitter, Kate Vandyke, Christopher G. Schultz, Deborah White, Timothy P. Hughes, and Andrew C. W. Zannettino|
|Abstract:||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.|
|Keywords:||Humans; Insulin Resistance; Piperazines; Pyrimidines; Protein Kinase Inhibitors; Absorptiometry, Photon; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Treatment Outcome; Analysis of Variance; Female; Male; Adiposity; Adiponectin; Leukemia, Myelogenous, Chronic, BCR-ABL Positive|
|Rights:||Copyright © 2010 by The Endocrine Society|
|Appears in Collections:||Medicine publications|
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