Fatty acids potentiate interleukin-1β toxicity in the β-cell line INS-1E

被引：18

作者：

Aarnes, M ^{[1
]}

Schonberg, S ^{[1
]}

Grill, V ^{[1
]}

机构：

[1] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Biol, N-7034 Trondheim, Norway

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2002年 / 296卷 / 01期

关键词：

fatty acids; beta-cells; INS-1; interleukin-1; beta; cytokines; insulin biosynthesis;

D O I：

10.1016/S0006-291X(02)00819-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Evidence for "lipotoxicity," i.e., negative effects of fatty acids (FA) on pancreatic beta-cells is incomplete. Here, we tested whether non-toxic concentrations of FA potentiate toxic effects of interleukin-1beta (IL-1beta). Culture of INS-1E clonal beta-cells for 2-6 days with 70 muM docosahexaenoic acid (DHA), eicosapentaenoic acid, arachidonic acid, 0.1 mM linoleic acid, or 0.1-0.2 mM oleic acid exerted no or minor negative effects on cell viability (MTT assay). Viability was reduced by 0.5 ng/ml IL-1beta. All tested FA significantly aggravated this effect after 6 days of culture. 1L-1beta also exerted negative effects on cellular insulin content and DHA and oleic acid aggravated these effects. L-NAME, an inhibitor of constitutive nitric oxide (NO) synthase, reduced the negative effects of IL-1beta per se but did not abolish the potentiating effects of FA. Conclusion: FA potentiate toxic effects of IL-1beta on beta-cells by mechanisms that include NO-independent ones. (C) 2002 Elsevier Science (USA). All rights reserved.

引用

页码：189 / 193

页数：5

共 21 条

[1] ESTABLISHMENT OF 2-MERCAPTOETHANOL-DEPENDENT DIFFERENTIATED INSULIN-SECRETING CELL-LINES [J].

ASFARI, M ;

JANJIC, D ;

MEDA, P ;

LI, GD ;

HALBAN, PA ;

WOLLHEIM, CB .

ENDOCRINOLOGY, 1992, 130 (01) :167-178

[2] Chronic exposure to free fatty acid reduces pancreatic β cell insulin content by increasing basal insulin secretion that is not compensated for by a corresponding increase in proinsulin biosynthesis translation [J].

Bollheimer, LC ;

Skelly, RH ;

Chester, MW ;

McGarry, JD ;

Rhodes, CJ .

JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (05) :1094-1101

[3] Expression profiling of palmitate- and oleate-regulated genes provides novel insights into the effects of chronic lipid exposure on pancreatic β-cell function [J].

Busch, AK ;

Cordery, D ;

Denyer, GS ;

Biden, TJ .

DIABETES, 2002, 51 (04) :977-987

[4] Identification of novel cytokine-induced genes in pancreatic β-cells by high-density oligonucleotide arrays [J].

Cardozo, AK ;

Kruhoffer, M ;

Leeman, R ;

Orntoft, T ;

Eizirik, DL .

DIABETES, 2001, 50 (05) :909-920

[5] Selection of insulinoma cell lines with resistance to interleukin-1β- and γ-interferon-induced cytotoxicity [J].

Chen, GX ;

Hohmeier, HE ;

Gasa, R ;

Tran, VV ;

Newgard, CB .

DIABETES, 2000, 49 (04) :562-570

[6] Expression of the transcription factor STAT-1α in insulinoma cells protects against cytotoxic effects of multiple cytokines [J].

Chen, GX ;

Hohmeier, HE ;

Newgard, CB .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (01) :766-772

[7] Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation [J].

Cnop, M ;

Hannaert, JC ;

Hoorens, A ;

Eizirik, DL ;

Pipeleers, DG .

DIABETES, 2001, 50 (08) :1771-1777

[8] Free fatty acid-induced inhibition of glucose and insulin-like growth factor I-induced deoxyribonucleic acid synthesis in the pancreatic β-cell line INS-1 [J].

Cousin, SP ;

Hügl, SR ;

Wrede, CE ;

Kajio, H ;

Myers, MG ;

Rhodes, CJ .

ENDOCRINOLOGY, 2001, 142 (01) :229-240

[9] STIMULATION OF INSULIN SECRETION BY INFUSION OF FREE FATTY ACIDS [J].

CRESPIN, SR ;

GREENOUGH, WB ;

STEINBERG, D .

JOURNAL OF CLINICAL INVESTIGATION, 1969, 48 (10) :1934-+

[10] INTERLEUKIN-1-BETA INDUCES THE EXPRESSION OF AN ISOFORM OF NITRIC-OXIDE SYNTHASE IN INSULIN-PRODUCING CELLS, WHICH IS SIMILAR TO THAT OBSERVED IN ACTIVATED MACROPHAGES [J].

EIZIRIK, DL ;

CAGLIERO, E ;

BJORKLUND, A ;

WELSH, N .

FEBS LETTERS, 1992, 308 (03) :249-252

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