Suppression of Transcription Factor PDX-1/IPF1/STF-1/IDX-1 Causes No Decrease in Insulin mRNA in MIN6 Cells

Kajimoto, Yoshitaka; Watada, Hirotaka; Matsuoka, Taka-aki; Kaneto, Hideaki; Fujitani, Yoshio; Miyazaki, Jun-ichi; Yamasaki, Yoshimitsu

doi:https://doi.org/10.1172/JCI119712

Suppression of Transcription Factor PDX-1/IPF1/STF-1/IDX-1 Causes No Decrease in Insulin mRNA in MIN6 Cells

Kajimoto, Yoshitaka; Watada, Hirotaka; Matsuoka, Taka-aki et al.

Journal of Clinical Investigation, 1997, 100(7), 1840-1846

アクセス数:813件（2025-07-11 23:28 集計）

固定URL: https://hdl.handle.net/11094/23107

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タイトル	Suppression of Transcription Factor PDX-1/IPF1/STF-1/IDX-1 Causes No Decrease in Insulin mRNA in MIN6 Cells
著者	NRID 1000060301256 1000060301256 著者名 Kajimoto, Yoshitaka
	NRID 1000060343480 1000060343480 著者名 Watada, Hirotaka
	NRID 1000010379258 1000010379258 著者名 Matsuoka, Taka-aki
	NRID 1000080448034 1000080448034 著者名 Kaneto, Hideaki
	NRID 1000030433783 1000030433783 著者名 Fujitani, Yoshio
	NRID 1000080229830 1000080229830 著者名 Miyazaki, Jun-ichi
	NRID 1000040201834 1000040201834 著者名 Yamasaki, Yoshimitsu
キーワード等	gene expression regulation
	transcription factors
	homeodomain protein
	antisense oligodeoxynucleotide
抄録	The insulin gene transcription factor PDX-1/IPF1/STF-1/ IDX-1 plays a key role in directing beta cell-specific gene expressions. Recently, impairment of PDX-1 expression or activity has been observed in beta cell-derived HIT cells cultured under high glucose concentrations, and this has been suggested as a possible cause of the decrease in insulin gene transcription. To investigate the pathophysiological significance of PDX-1 as a determinant of the rate of insulin gene transcription, we suppressed its expression in beta cell-derived MIN6 cells using an antisense oligodeoxynucleotide (ODN) and searched for possible changes in the beta cell-specific gene expression. Treatment of MIN6 cells with an 18-mer phosphorothioate ODN complementary to a sequence starting at the translation initiation codon of PDX-1 caused a potent, concentration-dependent reduction in PDX-1 expression; addition of 2 microM antisense ODN could reduce PDX-1 expression to 14+/-4% of the control. There was also a decrease in its DNA binding to the insulin gene A element. Despite such suppression of PDX-1, Northern blot analysis revealed no decrease in the amount of insulin mRNA in the MIN6 cells. Similarly, no changes were detected in the transcription of the glucokinase or islet amyloid polypeptide gene, for which PDX-1 was shown to function as a transcription factor. Thus, our findings dispute the physiological significance of PDX-1 in determining the rate of insulin gene transcription. This means that other components constituting the transcription-controlling machinery need to be evaluated in order to understand the molecular basis of impaired insulin biosynthesis such as that observed due to glucose toxicity.
出版者	American Society for Clinical Investigation
収録物名	Journal of Clinical Investigation
巻(号)	100(7)
ページ	1840-1846
刊行年月	1997-10
言語	英語
ハンドルURL	https://hdl.handle.net/11094/23107
PISSN	00219738
NCID	AA00695520
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1172/JCI119712
アクセス権	open access
権利情報	Copyright © 1997 The American Society for Clinical Investigation
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Clinical Investigation. 1997, 100(7), p. 1840-1846
DC.title	Suppression of Transcription Factor PDX-1/IPF1/STF-1/IDX-1 Causes No Decrease in Insulin mRNA in MIN6 Cells
DC.creator	Kajimoto, Yoshitaka
	Watada, Hirotaka
	Matsuoka, Taka-aki
	Kaneto, Hideaki
	Fujitani, Yoshio
	Miyazaki, Jun-ichi
	Yamasaki, Yoshimitsu
DC.publisher	American Society for Clinical Investigation
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	1997-10
DC.identifier	https://doi.org/10.1172/JCI119712
DC.subject	gene expression regulation
	transcription factors
	homeodomain protein
	antisense oligodeoxynucleotide
DCTERMS.abstract	The insulin gene transcription factor PDX-1/IPF1/STF-1/ IDX-1 plays a key role in directing beta cell-specific gene expressions. Recently, impairment of PDX-1 expression or activity has been observed in beta cell-derived HIT cells cultured under high glucose concentrations, and this has been suggested as a possible cause of the decrease in insulin gene transcription. To investigate the pathophysiological significance of PDX-1 as a determinant of the rate of insulin gene transcription, we suppressed its expression in beta cell-derived MIN6 cells using an antisense oligodeoxynucleotide (ODN) and searched for possible changes in the beta cell-specific gene expression. Treatment of MIN6 cells with an 18-mer phosphorothioate ODN complementary to a sequence starting at the translation initiation codon of PDX-1 caused a potent, concentration-dependent reduction in PDX-1 expression; addition of 2 microM antisense ODN could reduce PDX-1 expression to 14+/-4% of the control. There was also a decrease in its DNA binding to the insulin gene A element. Despite such suppression of PDX-1, Northern blot analysis revealed no decrease in the amount of insulin mRNA in the MIN6 cells. Similarly, no changes were detected in the transcription of the glucokinase or islet amyloid polypeptide gene, for which PDX-1 was shown to function as a transcription factor. Thus, our findings dispute the physiological significance of PDX-1 in determining the rate of insulin gene transcription. This means that other components constituting the transcription-controlling machinery need to be evaluated in order to understand the molecular basis of impaired insulin biosynthesis such as that observed due to glucose toxicity.
DC.rights	Copyright © 1997 The American Society for Clinical Investigation
DC.format	23107
citation_title	Suppression of Transcription Factor PDX-1/IPF1/STF-1/IDX-1 Causes No Decrease in Insulin mRNA in MIN6 Cells
citation_author	Kajimoto, Yoshitaka
	Watada, Hirotaka
	Matsuoka, Taka-aki
	Kaneto, Hideaki
	Fujitani, Yoshio
	Miyazaki, Jun-ichi
	Yamasaki, Yoshimitsu
citation_publisher	American Society for Clinical Investigation
citation_language	英語
citation_date	1997-10
citation_journal_title	Journal of Clinical Investigation
citation_volume	100
citation_issue	7
citation_firstpage	1840
citation_lastpage	1846
citation_doi	https://doi.org/10.1172/JCI119712
citation_public_url	https://hdl.handle.net/11094/23107

Suppression of Transcription Factor PDX-1/IPF1/STF-1/IDX-1 Causes No Decrease in Insulin mRNA in MIN6 Cells

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