Differential regulation of adipocytokine mRNAs by rosiglitazone in db/db mice.
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 (P < 0.001), 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% (P < 0.001) 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.
Moore
G B
GB
Department of Vascular Biology, GlaxoSmithKline, Harlow, Essex CM19 5AW, United Kingdom. Gary_B_Moore@gsk.com
Chapman
H
H
Holder
J C
JC
Lister
C A
CA
Piercy
V
V
Smith
S A
SA
Clapham
J C
JC
D052242:Adiponectin; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006729:Hormones, Ectopic / Q000096:biosynthesis / Q000235:genetics; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008820:Mice, Obese; D020932:Nerve Growth Factor; D010627:Phenethylamines / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D052243:Resistin; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D052242:Adiponectin; D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D006729:Hormones, Ectopic; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D010627:Phenethylamines; D011506:Proteins; D011743:Pyrimidines; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D052243:Resistin; C499623:Retn protein, mouse; C413576:Retnla protein, mouse; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; C006253:pirinixic acid; D020932:Nerve Growth Factor; C063157:BRL 35135