Tohoku J. Exp. Med., 2002, 197 (3)

Troglitazone Ameliorates Abnormal Activity of Protein Tyrosine
Phosphatase in Adipose Tissues of Otsuka
Long-Evans Tokushima Fatty Rats

SEIICHI TAGAMI, TOSHIRO HONDA, HARUHIKO YOSHIMURA, HIDEAKI HOMMA,¹
KOSEI OHNO,¹ HAJIME IDE,¹ SHINJI SAKAUE and YOSHIKAZU KAWAKAMI

The First Department of Medicine, Hokkaido University School of Medicine, Sapporo 060-8638, and
¹Depertment of Clinical Physiology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido,
Ishikari-Tobetsu, Hokkaido 061-0293

Protein tyrosine phosphatases (PTPases) play an essential role in the regulation of steady-state phosphorylation of the insulin receptor and other proteins in the insulin signaling pathway. To determine the role of PTPases in adipose tissue in the development into an insulin-resistant state, we examined PTPase activities and protein levels of three major candidate PTPases in adipose tissues of 26-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Particulate PTPase activities in visceral and epididymal adipose tissues of OLETF rats were increased compared to those in Long-Evans Tokushima Otsuka (LETO) rats, non-insulin-resistant controls. Cytosolic PTPase activities in these tissues were conversely decreased in OLETF rats. In subcutaneous adipose tissues, those changes were not observed. Western blot analysis showed that the amounts of leukocyte antigen-related PTPase (LAR), PTPase 1B (PTP1B), and src homology 2-containing PTPase (SH-PTP2) were increased in particulate fractions of visceral and epididymal fat of OLETF rats. On the other hand, those in the cytosolic fractions were slightly decreased. Troglitazone was administered to OLETF rats to examine the effect of the drug on the changes in PTPase activity and distribution. Troglitazone treatment restored those alterations in PTPase activity in the particulate fraction and the amounts of LAR, PTP1B and SH-PTP2 in both fractions of visceral and epididymal adipose tissues of OLETF rats. Although it remains unknown whether such effects of troglitazone are mediated by peroxisome proliferator-activated receptor g, these data provide useful information for understanding the significance of PTPase in insulin-resistant rats and the molecular mechanism of troglitazone action.

Keywords —— troglitazone; Otsuka Long-Evans Tokushima Fatty (OLETF) rat; insulin resistance; protein tyrosine phosphatase (PTPase); adipose tissue

© 2002 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2002, 197, 169-181

Address for reprints: Dr. Shinji Sakaue, The First Department of Medicine, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.

e-mail: sakaue-s@tb3.so-net.ne.jp