Deficiency of transcription factor Nkx6.1 does not prevent insulin secretion in INS-1E cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F23%3A00570547" target="_blank" >RIV/67985823:_____/23:00570547 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1038/s41598-023-27985-7" target="_blank" >https://doi.org/10.1038/s41598-023-27985-7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-023-27985-7" target="_blank" >10.1038/s41598-023-27985-7</a>

Result language

angličtina

Original language name

Deficiency of transcription factor Nkx6.1 does not prevent insulin secretion in INS-1E cells

Original language description

Pancreatic-beta-cell-specifying transcription factor Nkx6.1, indispensable for embryonic development of the pancreatic epithelium and commitment to beta-cell lineage, directly controls the expression of a glucose transporter (Glut2), pyruvate carboxylase (Pcx), and genes for insulin processing (endoplasmic reticulum oxidoreductase-1 beta, Ero1lb, zinc transporter-8, Slc30a8). The Nkx6.1 decline in aging diabetic Goto-Kakizaki rats contributes to beta-cell trans-differentiation into delta-cells. Elucidating further Nkx6.1 roles, we studied Nkx6.1 ablation in rat INS-1E cells, prepared by CRISPR/Cas9 gene editing from single colonies. INS-1E(Nkx6.1-/-) cells exhibited unchanged glucose-stimulated insulin secretion (GSIS), moderately decreased phosphorylating/non-phosphorylating respiration ratios at high glucose, unchanged but delayed ATP-elevation responses to glucose, delayed uptake of fluorescent glucose analog, but slightly improved cytosolic Ca2+-oscillations, induced by glucose, despite approximately halved Glut2, Pcx, Ero1lb, and Slc30a8 expression, and reduced nuclear receptors Nr4a1 and Nr4a3. Thus, ATP synthesis was time-compensated, despite the delayed GLUT2-mediated glucose uptake and crippled pyruvate-malate redox shuttle (owing to the PCX-deficiency) in INS-1E(Nkx6.1-/-) cells. Nkx6.1 thus controls the expression of genes that are not essential for acute insulin secretion, the function of which can be compensated for. Considerations that Nkx6.1 deficiency is an ultimate determinant of beta-cell pathology beyond cell trans-(de-)differentiation or beta-cell identity are not supported by our results.n

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

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

2045-2322

Volume of the periodical

13

Issue of the periodical within the volume

1

Country of publishing house

DE - GERMANY

Number of pages

13

Pages from-to

683

UT code for WoS article

000968670400067

EID of the result in the Scopus database

2-s2.0-85146277818