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Pioglitazone Rapidly Increases Serum Adiponectin Levels in Men With Normal Glucose Tolerance

¹ Department of Endocrinology, Metabolism, and Nephrology, Kochi Medical School, Kochi University, Nankoku, Japan
² Department of Internal Medicine, Kochi Prefectural Aki Hospital, Aki, Japan

Address correspondence to Yukio Ikeda, MD, PhD, Department of Endocrinology, Metabolism, and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan. E-mail: ikeday{at}kochi-u.ac.jp

The thiazolidinedione class of antidiabetes drugs has various pleiotropic effects on cardiovascular diseases and lipid metabolism (1). Thiazolidinediones including pioglitazone have been shown to increase circulating adiponectin in diabetic subjects, although the mechanism is not well understood (2,3). Since, in previous studies, adiponectin levels in diabetic patients were evaluated after 3 weeks of pioglitazone treatment, elevated adiponectin may be, in part, secondary to improved lipid and glucose handling in these studies. In this study, we examined short-term effects of pioglitazone on serum adiponectin in nondiabetic subjects to assess the effect of pioglitazone independently of glycolipid metabolism.

The study comprised 10 men aged 28–42 years (mean ± SE age 34 ± 2 years) with normal glucose tolerance, which was confirmed by a 75-g oral glucose tolerance test. Subjects gave written informed consent, and the study was approved by the institutional review board of the University of Kochi Medical School. Study participants were treated with 30 mg/day pioglitazone for 14 days, and fasting blood samples were obtained at baseline and at days 3, 7, 10, and 14 of pioglitazone treatment. The serum levels of total and high–molecular weight (HMW) adiponectin were measured using commercially available enzyme-linked immunosorbent assay kits (Otsuka Pharmaceuticals, Tokyo, Japan and Fujirebio, Tokyo, Japan, respectively).

Total and HMW adiponectin levels both rapidly increased within 3 days of pioglitazone treatment in all subjects and continued to increase throughout the study (total adiponectin 6.6 ± 1.0, 7.9 ± 1.2, 9.9 ± 1.6, 11.8 ± 1.9, and 13.7 ± 2.2 µg/ml [P < 0.05, repeated-measures ANOVA] and HMW adiponectin 4.3 ± 0.8, 5.2 ± 1.0, 7.0 ± 1.3, 8.4 ± 1.5, and 10.4 ± 1.9 µg/ml [P < 0.05] at days 0, 3, 7, 10, and 14, respectively). In addition, the HMW–to–total adiponectin ratio, which may be a useful predictor of insulin resistance and metabolic syndrome (4), was significantly increased after 14 days (0.59 ± 0.06 to 0.72 ± 0.04, P < 0.01). On the other hand, pioglitazone treatment for 14 days did not change fasting plasma glucose (5.4 ± 0.1 to 5.4 ± 0.1 mmol/l), C-reactive protein (0.31 ± 0.07 to 0.30 ± 0.07 mg/l), or lipid profile (data not shown). Small decreases in fasting plasma insulin (7.0 ± 0.7 to 6.3 ± 0.8 µU/ml), homeostasis model assessment of insulin resistance (1.7 ± 0.2 to 1.5 ± 0.2), and leptin levels (4.2 ± 0.5 to 3.4 ± 0.3 ng/ml) were detected after 14 days, but they were not statistically significant. We cannot overlook the possibility that the combination of these minor metabolic effects may contribute to the increased adiponectin; however, these parameters had not changed after 7 days pioglitazone treatment, when adiponectin levels were already elevated (data not shown).

Thus, pioglitazone rapidly increases serum adiponectin levels, which precedes changes in the status of glycolipid metabolism or inflammation. Our data strongly support the primary effect of pioglitazone on the regulation of circulating adiponectin.

References

1. Yki-Järvinen H: Thiazolidinediones. N Engl J Med 351:1106–1118, 2004[Free Full Text]
   
2. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K: Adiponectin and adiponectine receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116:1784–1792, 2006[Medline]
   
3. Kadowaki T, Yamauchi T: Adiponectin and adiponectin receptors. Endocr Rev 26:439–451, 2005[Abstract/Free Full Text]
   
4. Hara K, Horikoshi M, Yamauchi T, Yago H, Miyazaki O, Ebinuma H, Imai Y, Nagai R, Kadowaki T: Measurement of the high–molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care 29:1357–1362, 2006[Abstract/Free Full Text]
   

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This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ikeda, Y. Articles by Hashimoto, K. Search for Related Content PubMed PubMed Citation Articles by Ikeda, Y. Articles by Hashimoto, K. Social Bookmarking                What's this?