Insulin downregulates angiopoietin-like protein 4 mRNA in 3T3-L1 adipocytes.
Angiopoietin-like protein 4 (angptl4) is mainly secreted from adipose tissue and inhibits lipoprotein lipase activity. The expression and plasma levels of angptl4 are increased by fasting. To clarify its regulation in diabetes and metabolic syndrome, we investigated the effect of insulin on angptl4 mRNA expression in 3T3-L1 adipocytes by using quantitative real-time PCR. Insulin suppressed angptl4 mRNA expression in time- and dose-dependent manners, and the inhibitory effect was attenuated by a RNA synthesis inhibitor actinomycin D and a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Adenoviral-mediated overexpression of forkhead transcription factor Foxo1 increased angptl4 mRNA expression, and insulin significantly suppressed its effect. In addition, insulin failed to decrease angptl4 mRNA expression in an insulin-resistant state induced by TNF-alpha in 3T3-L1 adipocytes. These results suggest that insulin downregulates angptl4 mRNA expression via PI3K/Foxo1 pathway in 3T3-L1 adipocytes, and that the reduction of angptl4 mRNA by insulin is attenuated in insulin resistance.
Yamada
Tsutomu
T
Department of Endocrinology and Diabetes, Field of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ozaki
Nobuaki
N
Kato
Yoshiro
Y
Miura
Yoshitaka
Y
Oiso
Yutaka
Y
D041721:3T3-L1 Cells; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D000818:Animals; D001798:Blood Proteins / Q000235:genetics*; D002867:Chromones / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D001798:Blood Proteins; D002867:Chromones; D005419:Flavonoids; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D007328:Insulin; D009025:Morpholines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D003513:Cycloheximide; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one