Abstract
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.
MeSH terms
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Adiponectin / blood
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Adiponectin / genetics
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Adiponectin / metabolism
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Adipose Tissue / drug effects*
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Adipose Tissue / metabolism
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Adrenergic beta-3 Receptor Agonists*
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Adrenergic beta-Agonists / administration & dosage
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Adrenergic beta-Agonists / pharmacology*
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Animals
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Blood Glucose / drug effects
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Body Weight
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Diabetes Mellitus / drug therapy*
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Diabetes Mellitus / etiology
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Diabetes Mellitus / metabolism
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Diabetes Mellitus / physiopathology
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Dietary Fats / administration & dosage
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Dioxoles / administration & dosage
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Dioxoles / pharmacology*
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Disease Models, Animal
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Eating
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Hypoglycemic Agents / administration & dosage
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Hypoglycemic Agents / pharmacology*
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Injections, Subcutaneous
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Insulin / blood
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Insulin Resistance
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Lipids / blood
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Male
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Mice
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Obesity / complications
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Obesity / drug therapy*
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Obesity / metabolism
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Obesity / physiopathology
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Receptors, Adiponectin / blood
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Receptors, Adiponectin / genetics
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Receptors, Adiponectin / metabolism*
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Receptors, Adrenergic, beta-3 / genetics
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Receptors, Adrenergic, beta-3 / metabolism
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Tumor Necrosis Factor-alpha / blood
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Tumor Necrosis Factor-alpha / metabolism*
Substances
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Adiponectin
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Adipoq protein, mouse
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Adrenergic beta-3 Receptor Agonists
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Adrenergic beta-Agonists
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Blood Glucose
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Dietary Fats
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Dioxoles
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Hypoglycemic Agents
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Insulin
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Lipids
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Receptors, Adiponectin
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Receptors, Adrenergic, beta-3
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Tumor Necrosis Factor-alpha
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disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate