Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

<a href="/en/project/GA16-06700S" target="_blank" >GA16-06700S: Molecular mechanism of insulin secretion</a><br>

Continuities

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

Publication year

2018

Confidentiality

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

Name of the periodical

Molecules

ISSN

1420-3049

e-ISSN

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Volume of the periodical

23

Issue of the periodical within the volume

6

Country of publishing house

CH - SWITZERLAND

Number of pages

31

Pages from-to

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UT code for WoS article

000435875400244

EID of the result in the Scopus database

2-s2.0-85048951372