0493406 - FGÚ 2019 RIV CH eng J - Článek v odborném periodiku
Ježek, Petr - Jabůrek, Martin - Holendová, Blanka - Plecitá-Hlavatá, Lydie
Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity.
Molecules. Roč. 23, č. 6 (2018), č. článku 1483. E-ISSN 1420-3049
Grant CEP: GA ČR(CZ) GA16-06700S
Institucionální podpora: RVO:67985823
Klíčová slova: fatty acids * fatty acid-stimulated insulin secretion * GPR40 * pancreatic beta-cells * oxidative stress * lipotoxicity * type 2 diabetes * low-grade inflammation
Obor OECD: Endocrinology and metabolism (including diabetes, hormones)
Impakt faktor: 3.060, rok: 2018

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.
Trvalý link: http://hdl.handle.net/11104/0286770