The effects of beta(3)-adrenoceptor agonist CL-316,243 on adiponectin, adiponectin receptors and tumor necrosis factor-alpha expressions in adipose tissues of obese diabetic KKAy mice.
We investigated the effects of beta(3)-adrenoceptor agonist, 5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL-316,243) in obese diabetic KKAy mice. Two weeks' subcutaneous administration of CL-316,243 reduced serum levels of glucose, insulin, triglyceride, free fatty acid and tumor necrosis factor-alpha (TNF-alpha), and increased adiponectin. Adiponectin, adiponectin receptors and beta(3)-adrenoceptor mRNA expressions were reduced in epididymal white adipose tissue in KKAy mice, and CL-316,243 recovered these mRNA expressions. Meanwhile, CL-316,243 suppressed the overexpressed mRNA level of TNF-alpha in both epididymal white adipose tissue and brown adipose tissue. These data suggest that the normalization of adiponectin, adiponectin receptors and TNF-alpha may result in the amelioration of obesity-induced insulin resistance.
Fu
Ling
L
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Isobe
Kazumasa
K
Zeng
Qin
Q
Suzukawa
Kazumi
K
Takekoshi
Kazuhiro
K
Kawakami
Yasushi
Y
D052242:Adiponectin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D004041:Dietary Fats / Q000008:administration & dosage; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004435:Eating; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D054419:Receptors, Adiponectin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*
D052242:Adiponectin; C499919:Adipoq protein, mouse; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D004041:Dietary Fats; D004149:Dioxoles; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D054419:Receptors, Adiponectin; D022702:Receptors, Adrenergic, beta-3; D014409:Tumor Necrosis Factor-alpha; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate