A large-scale functional analysis of genes expressed differentially in insulin secreting MIN6 sublines with high versus mildly reduced glucose-responsiveness

Aya Tanaka, Minami Kosuda, Midori Yamana, Asami Furukawa, Akiko Nagasawa, Midori Fujishiro, Genta Kohno, Hisamitsu Ishihara

研究成果: ジャーナルへの寄稿記事査読

3 被引用数 (Scopus)

抄録

Molecular mechanisms of glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells are not fully understood. GSIS deteriorations are believed to underlie the pathogenesis of type 2 diabetes mellitus. By comparing transcript levels of 3 insulin secreting MIN6 cell sublines with strong glucose-responsiveness and 3 with mildly reduced responsiveness, we identified 630 differentially expressed genes. Using our recently developed system based on recombinase-mediated cassette exchange, we conducted large-scale generation of stable clones overexpressing such genes in the doxycycline-regulated manner. We found that overexpressions of 18, out of 83, genes altered GSIS. Sox11 ((sex determining region Y)-box 11) was selected to confirm its roles in regulating insulin secretion, and the gene was subjected to shRNA-mediated suppression. While Sox11 overexpression decreased GSIS, its suppression increased GSIS, confirming the role of Sox11 as a negative regulator of insulin secretion. Furthermore, metabolic experiments using radiolabelled glucose showed Sox11 to participate in regulating glucose metabolism. Our data suggested that overexpression screening is a feasible option for systemic functional testing to identify important genes in GSIS.

本文言語英語
論文番号5654
ジャーナルScientific Reports
13
1
DOI
出版ステータス出版済み - 12月 2023

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