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Involvement of the TLR4 (Toll-like receptor4) signaling pathway in palmitate-induced INS-1 beta cell death

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Abstract

Fatty acid-induced cytotoxicity is believed to recapitulate lipotoxicity seen in obese type-2 diabetes, and, thus, contribute to beta cell loss in the disease. These studies were initiated to determine whether the Toll-like receptor (TLR) signaling pathway was involved in palmitate-induced beta cell death. Treatment of INS-1 beta cells with palmitate enhanced interaction between TLR and myeloid differentiation factor88 (MyD88). Concomitant with TLR/MyD88 interaction, the level of phospho-C-Jun N-terminal kinase (phospho-JNK) showed an increase; however, the level of inhibitory factor kappa B alpha (IκBα) showed a decrease. Gene knockdown of TLR4 prevented palmitate-induced INS-1 cell death, while knockdown of TLR2 did not. In addition, gene knockdown of TLR4 prevented palmitate-induced increase of phospho-JNK and decrease of IκBα. JNK inhibitor SP60125 significantly protected against palmitate-induced INS-1 cell death, while IκB kinase (IKK) inhibitor acetylsalicylate did not. These data suggest involvement of JNK activation through the TLR4 signaling pathway in palmitate-induced INS-1 beta cell death.

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Acknowledgments

This study was supported by grants from the Korea Research Foundation (KRF 2009-0072584) and Gyunggi Regional Research Center (GRRC).

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Authors and Affiliations

  1. Institutes for Medical Sciences, Ajou University School of Medicine, Suwon, 442-749, Republic of Korea

    Sung-Mi Lee, Sung-E Choi, Ji-Hyun Lee, Jung-Jin Lee, Ik-Rak Jung, Soo-Jin Lee & Yup Kang

  2. Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, 442-749, Republic of Korea

    Kwan-Woo Lee

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  1. Sung-Mi Lee
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Correspondence to Yup Kang.

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Sung-Mi Lee, Sung-E Choi and Ji-Hyun Lee are contributed equally to this work.

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Lee, SM., Choi, SE., Lee, JH. et al. Involvement of the TLR4 (Toll-like receptor4) signaling pathway in palmitate-induced INS-1 beta cell death. Mol Cell Biochem 354, 207–217 (2011). https://doi.org/10.1007/s11010-011-0820-7

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