NEUROD1 Is Required for the Early alpha and beta Endocrine Differentiation in the Pancreas

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F21%3A00548733" target="_blank" >RIV/86652036:_____/21:00548733 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.mdpi.com/1422-0067/22/13/6713" target="_blank" >https://www.mdpi.com/1422-0067/22/13/6713</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms22136713" target="_blank" >10.3390/ijms22136713</a>

Jazyk výsledku

angličtina

Název v původním jazyce

NEUROD1 Is Required for the Early alpha and beta Endocrine Differentiation in the Pancreas

Popis výsledku v původním jazyce

Diabetes is a metabolic disease that involves the death or dysfunction of the insulin-secreting beta cells in the pancreas. Consequently, most diabetes research is aimed at understanding the molecular and cellular bases of pancreatic development, islet formation, beta-cell survival, and insulin secretion. Complex interactions of signaling pathways and transcription factor networks regulate the specification, growth, and differentiation of cell types in the developing pancreas. Many of the same regulators continue to modulate gene expression and cell fate of the adult pancreas. The transcription factor NEUROD1 is essential for the maturation of beta cells and the expansion of the pancreatic islet cell mass. Mutations of the Neurod1 gene cause diabetes in humans and mice. However, the different aspects of the requirement of NEUROD1 for pancreas development are not fully understood. In this study, we investigated the role of NEUROD1 during the primary and secondary transitions of mouse pancreas development. We determined that the elimination of Neurod1 impairs the expression of key transcription factors for alpha- and beta-cell differentiation, beta-cell proliferation, insulin production, and islets of Langerhans formation. These findings demonstrate that the Neurod1 deletion altered the properties of alpha and beta endocrine cells, resulting in severe neonatal diabetes, and thus, NEUROD1 is required for proper activation of the transcriptional network and differentiation of functional alpha and beta cells.

Název v anglickém jazyce

NEUROD1 Is Required for the Early alpha and beta Endocrine Differentiation in the Pancreas

Popis výsledku anglicky

Diabetes is a metabolic disease that involves the death or dysfunction of the insulin-secreting beta cells in the pancreas. Consequently, most diabetes research is aimed at understanding the molecular and cellular bases of pancreatic development, islet formation, beta-cell survival, and insulin secretion. Complex interactions of signaling pathways and transcription factor networks regulate the specification, growth, and differentiation of cell types in the developing pancreas. Many of the same regulators continue to modulate gene expression and cell fate of the adult pancreas. The transcription factor NEUROD1 is essential for the maturation of beta cells and the expansion of the pancreatic islet cell mass. Mutations of the Neurod1 gene cause diabetes in humans and mice. However, the different aspects of the requirement of NEUROD1 for pancreas development are not fully understood. In this study, we investigated the role of NEUROD1 during the primary and secondary transitions of mouse pancreas development. We determined that the elimination of Neurod1 impairs the expression of key transcription factors for alpha- and beta-cell differentiation, beta-cell proliferation, insulin production, and islets of Langerhans formation. These findings demonstrate that the Neurod1 deletion altered the properties of alpha and beta endocrine cells, resulting in severe neonatal diabetes, and thus, NEUROD1 is required for proper activation of the transcriptional network and differentiation of functional alpha and beta cells.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA19-07378S" target="_blank" >GA19-07378S: Interakce ISLET1 a NEUROD1 ve vývoji a v patofyziologii endokrinní tkáně pankreatu</a><br>

Návaznosti

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

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

1422-0067

Svazek periodika

22

Číslo periodika v rámci svazku

13

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

16

Strana od-do

—

Kód UT WoS článku

000671289600001

EID výsledku v databázi Scopus

2-s2.0-85108258147