Mechanism of amelioration of insulin resistance by β3-adrenoceptor agonist AJ-9677 in the KK-Ay/Ta diabetic obese mouse model

被引：51

作者：

Kato, H ^{[1
]}

Ohue, M

Kato, K

Nomura, A

Toyosawa, K

Furutani, Y

Kimura, S

Kadowaki, T

机构：

[1] Dainippon Pharmaceut Co Ltd, Discovery Res Labs, Dept Pharmacol 3, Osaka 5640053, Japan

[2] Dainippon Pharmaceut Co Ltd, Res & Dev Coordinat, Osaka 5640053, Japan

[3] Dainippon Pharmaceut Co Ltd, Dept Toxicol, Dev Res Labs, Osaka 5640053, Japan

[4] Univ Tokyo, Grad Sch Med, Dept Metab Dis, Tokyo, Japan

来源：

DIABETES | 2001年 / 50卷 / 01期

关键词：

D O I：

10.2337/diabetes.50.1.113

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The mechanism by which the specific beta (3)-adrenoceptor agonist AJ-9677 relieves insulin resistance in vivo was investigated by studying its effects in the white and brown adipose tissues of the KK-A(y)/Ta diabetic obese mouse model. AJ-9677 reduced the total weight of white adipose tissues by reducing the size of the adipocytes, an effect associated with the normalization of tumor necrosis factor-alpha (TNF-alpha) and leptin expression levels. The levels of uncoupling protein (UCP)-1 mRNA in brown adipose tissue were increased threefold. AJ-9677 caused a marked increase (20- to 80-fold) in the expression of UCP-1 in white adipose tissues. The levels of UCP-2 mRNA were increased in both the white and brown adipose tissues of diabetic obese mice, and AJ-9677 further upregulated UCP-8 mRNA levels in brown adipose tissue, but reduced its levels in white adipose tissue. UCP-3 mRNA levels were not essentially changed by AJ-9677. However, AJ-9677 significantly (two- to four-fold) upregulated the GLUT4 mRNA and protein levels in white and brown adipose tissues and the gastrocnemius. The generation of small adipocytes, presumably mediated by increased expression of UCP-1 in addition to increased lipolysis in response to AJ-9677, was associated with decreased TNF-alpha and free fatty acid production and may be the mechanism of amelioration of insulin resistance in KK-A(y)/Ta diabetic obese mice.

引用

页码：113 / 122

页数：10

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