Troglitazone improves GLUT4 expression in adipose tissue in an animal model of obese type 2 diabetes mellitus

Furuta, Masahiko; Yano, Yutaka; Gabazza, Esteban C.; Araki-Sasaki, Rika; Tanaka, Takashi; Katsuki, Akira; Hori, Yasuko; Nakatani, Kaname; Sumida, Yasuhiro; Adachi, Yukihiko

« Previous Next »Diabetes Research and Clinical Practice
Volume 56, Issue 3 , Pages 159-171, June 2002

Troglitazone improves GLUT4 expression in adipose tissue in an animal model of obese type 2 diabetes mellitus

Masahiko Furuta
- Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan
Yutaka Yano
- Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan
- Corresponding author. Tel.: +81-59-232-1111; fax: +81-59-231-5223
Esteban C. Gabazza
- Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan
Rika Araki-Sasaki
- Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan
Takashi Tanaka
- Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan
Akira Katsuki
- Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan
Yasuko Hori
- Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan
Kaname Nakatani
- Department of Laboratory Medicine, Mie University School of Medicine, Mie, Japan
Yasuhiro Sumida
- Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan
Yukihiko Adachi
- Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan

Received 17 July 2001; received in revised form 19 November 2001; accepted 6 December 2001.

Abstract

Troglitazone has been shown to improve peripheral insulin resistance in type 2 diabetic patients and animal models. We examined the effect of troglitazone on the expression of glucose transporter 4 (GLUT4) in muscle and adipose tissue from Otsuka Long–Evans Tokushima Fatty (OLETF) rat, an animal model of obese type 2 diabetes mellitus. In addition, the effects of troglitazone on GLUT4 translocation and on glucose transport activity in adipocytes were also evaluated. Muscle and adipose tissues were isolated from 35-week-old male troglitazone-treated and untreated OLETF rats at a dose of 150 mg/kg per day for 14 days. In skeletal muscle, the protein and mRNA levels of GLUT4 were not significantly different between OLETF and control rats and they were not affected by troglitazone. On the other hand, GLUT4 protein and mRNA levels in adipose tissue from OLETF rats were significantly decreased (P<0.01) compared with control rats and they were significantly increased (1.5-fold, P<0.01) by troglitazone. Troglitazone had no major effect on GLUT4 translocation in adipocytes, but it significantly increased (1.4-fold, P<0.05) the basal and insulin-induced amounts of GLUT4 in plasma membrane (PM) in adipocytes from OLETF rats. Consistent with these results, the basal and insulin-induced glucose uptakes in adipocytes from troglitazone-treated OLETF rats were significantly increased (1.5-fold, P<0.05) compared with untreated OLETF rats. Our results suggest that troglitazone may exert beneficial effects on insulin resistance by increasing the expression of GLUT4 in adipose tissue.

Keywords: Troglitazone, GLUT4 expression, OLETF rat, Translocation, Diabetes mellitus