Nkx6.1 decline accompanies mitochondrial DNA reduction but subtle nucleoid size decrease in pancreatic islet beta-cells of diabetic Goto Kakizaki rats

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F17%3A00076207" target="_blank" >RIV/00023001:_____/17:00076207 - isvavai.cz</a>

Alternative codes found

RIV/67985823:_____/17:00485798

Result on the web

<a href="https://www.nature.com/articles/s41598-017-15958-6.pdf" target="_blank" >https://www.nature.com/articles/s41598-017-15958-6.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-017-15958-6" target="_blank" >10.1038/s41598-017-15958-6</a>

Result language

angličtina

Original language name

Nkx6.1 decline accompanies mitochondrial DNA reduction but subtle nucleoid size decrease in pancreatic islet beta-cells of diabetic Goto Kakizaki rats

Original language description

Hypertrophic pancreatic islets (PI) of Goto Kakizaki (GK) diabetic rats contain a lower number of beta-cells vs. non-diabetic Wistar rat PI. Remaining beta-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 &lt;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 &quot;nucleoids&quot; which were smaller by 25% (less diameters &gt;150 nm) in GK beta-cells. Eos-TFAM-visualized nucleoids, composed of 72% localized TFAM, were smaller by 10% (immunochemically by 3%). A theoretical similar to 70% decrease in cell nucleoid number (spatial density) was not observed, rejecting model of single mtDNA per nucleoid. The beta-cell maintenance factor Nkx6.1 mRNA and protein were declining with age (&gt;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 beta-cells.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific reports

ISSN

2045-2322

e-ISSN

—

Volume of the periodical

7

Issue of the periodical within the volume

November 15

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

"art. no. 15674"

UT code for WoS article

000415266100023

EID of the result in the Scopus database

—