Fetts�ureinduzierte -Zell-Apoptose

Eitel, Katrin; Staiger, Harald; Brendel, Mathias D.; Brandhorst, Heide; Bretzel, Reinhard G.; Häring, Hans‐Ulrich; Kellerer, Monika

doi:10.1007/s00063-003-1253-1

Cited by 8 publications

(2 citation statements)

References 26 publications

(29 reference statements)

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“…However, recent reports have demonstrated that the ability of fatty acids to cause apoptosis in the rat ␤-cell line RIN1046-38 and human islets is dependent on the degree of saturation. Whereas palmitic acid and stearic acid were pro-apoptotic when used at 1 mM for 24 h, linoleic acid, palmitoleic acid, and oleic acid did not cause apoptosis and actually protected the ␤-cells from apoptosis resulting from incubation with saturated fatty acids (35). Because a large range of both saturated and unsaturated fatty acids are agonists for GPR40, the primary role of the receptor may therefore not be mediation of the apoptotic effects of fatty acids.…”

Section: Fatty Acids As Ligands For Gpr40mentioning

confidence: 99%

The Orphan G Protein-coupled Receptor GPR40 Is Activated by Medium and Long Chain Fatty Acids

Briscoe¹,

Tadayyon²,

Andrews³

et al. 2003

Journal of Biological Chemistry

981

1,002

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GPR40 is a member of a subfamily of homologous G protein-coupled receptors that include GPR41 and GPR43 and that have no current function or ligand ascribed. Ligand fishing experiments in HEK293 cells expressing human GPR40 revealed that a range of saturated and unsaturated carboxylic acids with carbon chain lengths greater than six were able to induce an elevation of [Ca 2؉ ] i , measured using a fluorometric imaging plate reader. 5,8,11-Eicosatriynoic acid was the most potent fatty acid tested, with a pEC 50 of 5.7. G protein coupling of GPR40 was examined in Chinese hamster ovary cells expressing the G␣ q/i -responsive Gal4-Elk1 reporter system. Expression of human GPR40 led to a constitutive induction of luciferase activity, which was further increased by exposure of the cells to eicosatriynoic acid. Neither the constitutive nor ligandmediated luciferase induction was inhibited by pertussis toxin treatment, suggesting that GPR40 was coupled to G␣ q/11. Expression analysis by quantitative reverse transcription-PCR showed that GPR40 was specifically expressed in brain and pancreas, with expression in rodent pancreas being localized to insulin-producing ␤-cells. These data suggest that some of the physiological effects of fatty acids in pancreatic islets and brain may be mediated through a cell-surface receptor.

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Section: Fatty Acids As Ligands For Gpr40mentioning

confidence: 99%

The Orphan G Protein-coupled Receptor GPR40 Is Activated by Medium and Long Chain Fatty Acids

Briscoe¹,

Tadayyon²,

Andrews³

et al. 2003

Journal of Biological Chemistry

981

1,002

View full text Add to dashboard Cite

show abstract

“…Chronic treatment with high physiological levels of saturated FA, but not with mono-or polyunsaturated FA, triggers apoptosis in about 20% of cultured b-cells [94]. Chronic treatment with high physiological levels of saturated FA, but not with mono-or polyunsaturated FA, triggers apoptosis in about 20% of cultured b-cells [94].…”

Section: Molecular Mechanismsmentioning

confidence: 99%

Physiological and Pharmacological Regulation of Triacylglycerol Storage and Mobilization

Müller¹,

Petry²

2004

Lipases and Phospholipases in Drug Development

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Long-term exposure of INS-1 rat insulinoma cells to linoleic acid and glucose in vitro affects cell viability and function through mitochondrial-mediated pathways

Tuo

Wang

et al. 2010

Endocr

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Obesity with excessive levels of circulating free fatty acids (FFAs) is tightly linked to the incidence of type 2 diabetes. Insulin resistance of peripheral tissues and pancreatic β-cell dysfunction are two major pathological changes in diabetes and both are facilitated by excessive levels of FFAs and/or glucose. To gain insight into the mitochondrial-mediated mechanisms by which long-term exposure of INS-1 cells to excess FFAs causes β-cell dysfunction, the effects of the unsaturated FFA linoleic acid (C 18:2, n-6) on rat insulinoma INS-1 β cells was investigated. INS-1 cells were incubated with 0, 50, 250 or 500 μM linoleic acid/0.5% (w/v) BSA for 48 h under culture conditions of normal (11.1 mM) or high (25 mM) glucose in serum-free RPMI-1640 medium. Cell viability, apoptosis, glucose-stimulated insulin secretion, Bcl-2, and Bax gene expression levels, mitochondrial membrane potential and cytochrome c release were examined. Linoleic acid 500 μM significantly suppressed cell viability and induced apoptosis when administered in 11.1 and 25 mM glucose culture medium. Compared with control, linoleic acid 500 μM significantly increased Bax expression in 25 mM glucose culture medium but not in 11.1 mM glucose culture medium. Linoleic acid also dose-dependently reduced mitochondrial membrane potential (ΔΨm) and significantly promoted cytochrome c release from mitochondria in both 11.1 mM glucose and 25 mM glucose culture medium, further reducing glucose-stimulated insulin secretion, which is dependent on normal mitochondrial function. With the increase in glucose levels in culture medium, INS-1 β-cell insulin secretion function was deteriorated further. The results of this study indicate that chronic exposure to linoleic acid-induced β-cell dysfunction and apoptosis, which involved a mitochondrial-mediated signal pathway, and increased glucose levels enhanced linoleic acid-induced β-cell dysfunction.

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Fetts�ureinduzierte -Zell-Apoptose

Abstract: FFAs exert different effects on beta-cell survival. Saturated FFAs turned out to be pro-apoptotic, whereas unsaturated FFAs protected from saturated FFA-induced apoptosis. Furthermore, our data suggest an involvement of PKC-delta in apoptosis induced by saturated FFAs.

Cited by 8 publications

References 26 publications

The Orphan G Protein-coupled Receptor GPR40 Is Activated by Medium and Long Chain Fatty Acids

The Orphan G Protein-coupled Receptor GPR40 Is Activated by Medium and Long Chain Fatty Acids

Physiological and Pharmacological Regulation of Triacylglycerol Storage and Mobilization

Long-term exposure of INS-1 rat insulinoma cells to linoleic acid and glucose in vitro affects cell viability and function through mitochondrial-mediated pathways

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