ArticleScientific reports2017
Nkx6.1 decline accompanies mitochondrial DNA reduction but subtle nucleoid size decrease in pancreatic islet β-cells of diabetic Goto Kakizaki rats.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Mitochondrial development and remodeling occur at pancreatic progenitor stage during induction of stem cell-derived islet organoids.Frontiers in endocrinology · 2026Article
- Transcriptional coactivator MED15 is required for beta cell maturation.Nature communications · 2024Article
- Possible frequent multiple mitochondrial DNA copies in a single nucleoid in HeLa cells.Scientific reports · 2023Article
- Deficiency of transcription factor Nkx6.1 does not prevent insulin secretion in INS-1E cells.Scientific reports · 2023Article
- Review
- Of numbers and movement - understanding transcription factor pathogenesis by advanced microscopy.Disease models & mechanisms · 2020Review
- Contribution of Oxidative Stress and Impaired Biogenesis of Pancreatic β-Cells to Type 2 Diabetes.Antioxidants & redox signaling · 2019Article
- Organization of DNA in Mammalian Mitochondria.International journal of molecular sciences · 2019Review
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Authors and funding
9 authors.
Funding
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Abstract
Hypertrophic pancreatic islets (PI) of Goto Kakizaki (GK) diabetic rats contain a lower number of β-cells vs. non-diabetic Wistar rat PI. Remaining β-cells contain reduced mitochondrial (mt) DNA per nucleus (copy number), probably due to declining mtDNA replication machinery, decreased mt biogenesis or enhanced mitophagy. We confirmed mtDNA copy number decrease down to <30% in PI of one-year-old GK rats. Studying relations to mt nucleoids sizes, we employed 3D superresolution fluorescent photoactivable localization microscopy (FPALM) with lentivirally transduced Eos conjugate of mt single-stranded-DNA-binding protein (mtSSB) or transcription factor TFAM; or by 3D immunocytochemistry. mtSSB (binding transcription or replication nucleoids) contoured "nucleoids" which were smaller by 25% (less diameters >150 nm) in GK β-cells. Eos-TFAM-visualized nucleoids, composed of 72% localized TFAM, were smaller by 10% (immunochemically by 3%). A theoretical ~70% decrease in cell nucleoid number (spatial density) was not observed, rejecting model of single mtDNA per nucleoid. The β-cell maintenance factor Nkx6.1 mRNA and protein were declining with age (>12-fold, 10 months) and decreasing with fasting hyperglycemia in GK rats, probably predetermining the impaired mtDNA replication (copy number decrease), while spatial expansion of mtDNA kept nucleoids with only smaller sizes than those containing much higher mtDNA in non-diabetic β-cells.
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