Redox Homeostasis in Pancreatic beta-Cells: From Development to Failure

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F21%3A00542431" target="_blank" >RIV/67985823:_____/21:00542431 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/21:10428100

Výsledek na webu

<a href="https://www.mdpi.com/2076-3921/10/4/526" target="_blank" >https://www.mdpi.com/2076-3921/10/4/526</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/antiox10040526" target="_blank" >10.3390/antiox10040526</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Redox Homeostasis in Pancreatic beta-Cells: From Development to Failure

Popis výsledku v původním jazyce

Redox status is a key determinant in the fate of beta-cell. These cells are not primarily detoxifying and thus do not possess extensive antioxidant defense machinery. However, they show a wide range of redox regulating proteins, such as peroxiredoxins, thioredoxins or thioredoxin reductases, etc., being functionally compartmentalized within the cells. They keep fragile redox homeostasis and serve as messengers and amplifiers of redox signaling. beta-cells require proper redox signaling already in cell ontogenesis during the development of mature beta-cells from their progenitors. We bring details about redox-regulated signaling pathways and transcription factors being essential for proper differentiation and maturation of functional beta-cells and their proliferation and insulin expression/maturation. We briefly highlight the targets of redox signaling in the insulin secretory pathway and focus more on possible targets of extracellular redox signaling through secreted thioredoxin1 and thioredoxin reductase1. Tuned redox homeostasis can switch upon chronic pathological insults towards the dysfunction of beta-cells and to glucose intolerance. These are characteristics of type 2 diabetes, which is often linked to chronic nutritional overload being nowadays a pandemic feature of lifestyle. Overcharged beta-cell metabolism causes pressure on proteostasis in the endoplasmic reticulum, mainly due to increased demand on insulin synthesis, which establishes unfolded protein response and insulin misfolding along with excessive hydrogen peroxide production. This together with redox dysbalance in cytoplasm and mitochondria due to enhanced nutritional pressure impact beta-cell redox homeostasis and establish prooxidative metabolism. This can further affect beta-cell communication in pancreatic islets through gap junctions. In parallel, peripheral tissues losing insulin sensitivity and overall impairment of glucose tolerance and gut microbiota establish local proinflammatory signaling and later systemic metainflammation, i.e., low chronic inflammation prooxidative properties, which target beta-cells leading to their dedifferentiation, dysfunction and eventually cell death.

Název v anglickém jazyce

Redox Homeostasis in Pancreatic beta-Cells: From Development to Failure

Popis výsledku anglicky

Redox status is a key determinant in the fate of beta-cell. These cells are not primarily detoxifying and thus do not possess extensive antioxidant defense machinery. However, they show a wide range of redox regulating proteins, such as peroxiredoxins, thioredoxins or thioredoxin reductases, etc., being functionally compartmentalized within the cells. They keep fragile redox homeostasis and serve as messengers and amplifiers of redox signaling. beta-cells require proper redox signaling already in cell ontogenesis during the development of mature beta-cells from their progenitors. We bring details about redox-regulated signaling pathways and transcription factors being essential for proper differentiation and maturation of functional beta-cells and their proliferation and insulin expression/maturation. We briefly highlight the targets of redox signaling in the insulin secretory pathway and focus more on possible targets of extracellular redox signaling through secreted thioredoxin1 and thioredoxin reductase1. Tuned redox homeostasis can switch upon chronic pathological insults towards the dysfunction of beta-cells and to glucose intolerance. These are characteristics of type 2 diabetes, which is often linked to chronic nutritional overload being nowadays a pandemic feature of lifestyle. Overcharged beta-cell metabolism causes pressure on proteostasis in the endoplasmic reticulum, mainly due to increased demand on insulin synthesis, which establishes unfolded protein response and insulin misfolding along with excessive hydrogen peroxide production. This together with redox dysbalance in cytoplasm and mitochondria due to enhanced nutritional pressure impact beta-cell redox homeostasis and establish prooxidative metabolism. This can further affect beta-cell communication in pancreatic islets through gap junctions. In parallel, peripheral tissues losing insulin sensitivity and overall impairment of glucose tolerance and gut microbiota establish local proinflammatory signaling and later systemic metainflammation, i.e., low chronic inflammation prooxidative properties, which target beta-cells leading to their dedifferentiation, dysfunction and eventually cell death.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/GA20-00408S" target="_blank" >GA20-00408S: Redoxní signalizace beta buněk pankreatu při sekreci inzulinu a v rozvoji diabetu 2. typu</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

Antioxidants

ISSN

2076-3921

e-ISSN

2076-3921

Svazek periodika

10

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

30

Strana od-do

526

Kód UT WoS článku

000642727300001

EID výsledku v databázi Scopus

2-s2.0-85103137954