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

Autor: Tanaka A; Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi, 173-8610, Japan., Kosuda M; Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi, 173-8610, Japan., Yamana M; Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi, 173-8610, Japan., Furukawa A; Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi, 173-8610, Japan., Nagasawa A; Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi, 173-8610, Japan., Fujishiro M; Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi, 173-8610, Japan., Kohno G; Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi, 173-8610, Japan., Ishihara H; Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi, 173-8610, Japan. ishihara.hisamitsu@nihon-u.ac.jp.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Apr 06; Vol. 13 (1), pp. 5654. Date of Electronic Publication: 2023 Apr 06.
DOI: 10.1038/s41598-023-32589-2
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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