Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F18%3A00493406" target="_blank" >RIV/67985823:_____/18:00493406 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.3390/molecules23061483" target="_blank" >http://dx.doi.org/10.3390/molecules23061483</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules23061483" target="_blank" >10.3390/molecules23061483</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

Popis výsledku v původním jazyce

Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet beta-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the K-ATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2 gamma. Also, excessive dietary FAs stimulate intestine enterocyte incretin secretion, further elevating GSIS, even at low glucose levels, thus contributing to diabetic hyperinsulinemia. With overnutrition and obesity, the FA overload causes impaired GSIS by metabolic dysbalance, paralleled by oxidative and metabolic stress, endoplasmic reticulum stress and numerous pro-apoptotic signaling, all leading to decreased beta-cell survival. Lipotoxicity is exerted by saturated FAs, whereas omega-3 polyunsaturated FAs frequently exert antilipotoxic effects. FA-facilitated inflammation upon the recruitment of excess M1 macrophages into islets (over resolving M2 type), amplified by cytokine and chemokine secretion by beta-cells, leads to an inevitable failure of pancreatic beta-cells.

Název v anglickém jazyce

Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

Popis výsledku anglicky

Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet beta-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the K-ATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2 gamma. Also, excessive dietary FAs stimulate intestine enterocyte incretin secretion, further elevating GSIS, even at low glucose levels, thus contributing to diabetic hyperinsulinemia. With overnutrition and obesity, the FA overload causes impaired GSIS by metabolic dysbalance, paralleled by oxidative and metabolic stress, endoplasmic reticulum stress and numerous pro-apoptotic signaling, all leading to decreased beta-cell survival. Lipotoxicity is exerted by saturated FAs, whereas omega-3 polyunsaturated FAs frequently exert antilipotoxic effects. FA-facilitated inflammation upon the recruitment of excess M1 macrophages into islets (over resolving M2 type), amplified by cytokine and chemokine secretion by beta-cells, leads to an inevitable failure of pancreatic beta-cells.

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/GA16-06700S" target="_blank" >GA16-06700S: Molekulární mechanismus sekrece inzulinu</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Molecules

ISSN

1420-3049

e-ISSN

—

Svazek periodika

23

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

31

Strana od-do

—

Kód UT WoS článku

000435875400244

EID výsledku v databázi Scopus

2-s2.0-85048951372