1. Differential regulation of adipocytokine mRNAs by rosiglitazone in db/db mice
- Author
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John C. Clapham, Stephen A. Smith, Valerie Piercy, Helen Chapman, Gary B.T. Moore, Julie C. Holder, and Carolyn A. Lister
- Subjects
Agonist ,Blood Glucose ,medicine.medical_specialty ,medicine.drug_class ,Biophysics ,Adipose tissue ,Adipokine ,Mice, Obese ,Receptors, Cytoplasmic and Nuclear ,Biochemistry ,Rosiglitazone ,Mice ,Internal medicine ,Nerve Growth Factor ,Phenethylamines ,medicine ,Animals ,Hypoglycemic Agents ,Resistin ,RNA, Messenger ,Molecular Biology ,Adiponectin ,Chemistry ,Tumor Necrosis Factor-alpha ,nutritional and metabolic diseases ,Proteins ,Cell Biology ,Adrenergic beta-Agonists ,Thiazoles ,Endocrinology ,Pyrimidines ,Diabetes Mellitus, Type 2 ,Gene Expression Regulation ,Metabolic control analysis ,Protein Biosynthesis ,Hormones, Ectopic ,Intercellular Signaling Peptides and Proteins ,Tumor necrosis factor alpha ,Female ,Thiazolidinediones ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Transcription Factors - Abstract
The precise mechanism by which PPARgamma activation by thiazolidinediones (TZDs) improves insulin sensitivity is still unclear. Recent studies have focused on the role of adipocytokines in metabolic control and their regulation by TZDs. In this study, we compared the chronic effects of antihyperglycemic doses of the TZD rosiglitazone, the beta3-adrenoceptor agonist BRL-35135, and the PPARalpha agonist Wy-14,643 on the mRNA expression of adipocytokines in WAT of db/db mice. Rosiglitazone treatment decreased adiponectin and resistin mRNA levels by 57 and 72%, respectively (P0.001), with no effect on the level of TNFalpha or RELMalpha transcripts. In comparison, Wy-14,643 reduced adiponectin transcript levels by 31% (P = 0.015) while BRL-35135 increased RELMalpha mRNA expression by 245% (P0.001) without effect on the other transcripts. Our results indicate that although a reduction in adiponectin and resistin mRNA levels in WAT by rosiglitazone treatment of diabetic mice may contribute to the antidiabetic effects, an alteration in TNFalpha, adiponectin, resistin, or RELMalpha mRNA expression is not absolutely required for the regulation of blood glucose concentration in the db/db mouse.
- Published
- 2001