Počet záznamů: 1

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

SYSNO ASEP	0570547
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Deficiency of transcription factor Nkx6.1 does not prevent insulin secretion in INS-1E cells
Tvůrce(i)	Pavluch, Vojtěch (FGU-C)_{RID, ORCID} Engstová, Hana (FGU-C)_{RID, ORCID} Špačková, Jitka (FGU-C)_{RID, ORCID} Ježek, Petr (FGU-C)_{RID, ORCID}
Číslo článku	683
Zdroj.dok.	Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322 Roč. 13, č. 1 (2023)
Poč.str.	13 s.
Jazyk dok.	eng - angličtina
Země vyd.	DE - Německo
Klíč. slova	Nkx6.1 ; pancreatic-beta-cells ; GLUT2 ; pyruvate carboxylase ; glucose-stimulated insulin secretion
Obor OECD	Endocrinology and metabolism (including diabetes, hormones)
CEP	LX22NPO5104 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
	GA20-00408S GA ČR - Grantová agentura ČR
Způsob publikování	Open access
Institucionální podpora	FGU-C - RVO:67985823
UT WOS	000968670400067
EID SCOPUS	85146277818
DOI	10.1038/s41598-023-27985-7
Anotace	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.
Pracoviště	Fyziologický ústav
Kontakt	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Rok sběru	2024
Elektronická adresa	https://doi.org/10.1038/s41598-023-27985-7

Počet záznamů: 1