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Short-term but not long-term hypoglycaemia enhances plasma levels and hepatic expression of HSP72 in insulin-treated rats: an effect associated with increased IL-6 levels but not with IL-10 or TNF–α

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Abstract

The inducible expression of the 70-kDa heat shock proteins (HSP70) is associated with homeostatically stressful situations. Stresses involving sympathetic nervous system (SNS) activation, including α1-adrenergic agonists and physical exercise, are capable of inducing HSP70 expression and release of the HSP70 inducible form, HSP72. However, whether hypoglycaemia is capable of influencing HSP70 status under a stressful situation such as insulin-induced hypoglycaemia (IIH), which also involves SNS activation, is unsettled. Hence, we decided to investigate whether the predominant signal for HSP70 expression and delivery into the blood comes from either low glucose, high insulin, or both during short-term IIH (STIIH) and long-term IIH (LTIIH). Our data indicated that low glucose level (up to 1.56 ± 0.14 mM), but not insulin, is the triggering factor responsible for a dramatic rise in HSP72 plasma concentrations (from 0.15 ± 0.01 in fed state to 0.77 ± 0.13 ng/mL during hypoglycaemic episodes). This was observed in parallel with up to 7-fold increases in interleukin-6 (IL–6) but not interleukin-10 (IL–10) or tumour necrosis factor-α (TNF–α) at STIIH. Together, the observations may suggest that HSP72 is released under hypoglycaemic conditions as a part of the homeostatic stress response, whereas at long-term, both hypoglycaemia and insulin may influence HSP72 expression in the liver, but not in kidneys. Secreted extracellular HSP72 (eHSP72) may be purely a danger signal to all the tissues of the body for the enhancement of immune and metabolic surveillance state or actively participates in glycaemic control under stressful situations.

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Abbreviations

HSP70:

The 70 kDa family of heat shock proteins

IIH:

Insulin-induced hypoglycaemia

IL-6:

Interleukin-6

IL-10:

Interleukin-10

TNF–α:

Tumour necrosis factor alpha

STIIH:

Short-term IIH

LTIIH:

Long-term IIH

SNS:

Sympathetic nervous system

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Acknowledgments

This work was partially supported by grants received from the Brazilian National Council for Scientific and Technological Development (CNPq): grants from MCT/CNPq, MS/DECIT, CT-CIOTEC and CTSaúde, process #551097/2007–8, 563870/2010-9, 402626/2012-5 and 402364/2012-0, to PIHBJ and RBB; Fundação Araucária (to RBB). TGH was supported by a fellowship from Brazilian Federal Agency for the Support and Evaluation of Graduate (CAPES) while SPS and PRN were supported by fellowships from CNPq. All the authors have agreed to the submission and had final approval of the submitted and published versions.

Conflict of interest

The authors declare no conflict of interest and no competing interests such as consultancies, financial involvement, patent ownership, etc. in relation to the work described.

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Authors and Affiliations

  1. Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite 500, ICBS, 2° andar, Porto Alegre, RS, 90050-170, Brazil

    Mirna Stela Ludwig, Sofia Pizzato Scomazzon, Patrícia Renck Nunes & Paulo Ivo Homem de Bittencourt Jr.

  2. Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, PR, Brazil

    Vânia Cibele Minguetti-Câmara & Roberto Barbosa Bazotte

  3. Research Physiology Group, Post-Graduation Program in Integral Attention to Health, Department of Life Sciences, Regional University of the Northwest of Rio Grande do Sul State, Ijuí, RS, Brazil

    Thiago Gomes Heck

  4. National Institute of Hormones and Women’s Health (INCT), Porto Alegre, RS, Brazil

    Paulo Ivo Homem de Bittencourt Jr.

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  1. Mirna Stela Ludwig
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  2. Vânia Cibele Minguetti-Câmara
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Correspondence to Paulo Ivo Homem de Bittencourt Jr..

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Mirna Stela Ludwig, Vânia Cibele Minguetti-Câmara and Thiago Gomes Heck equally contributed to the present work.

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Ludwig, M.S., Minguetti-Câmara, V.C., Heck, T.G. et al. Short-term but not long-term hypoglycaemia enhances plasma levels and hepatic expression of HSP72 in insulin-treated rats: an effect associated with increased IL-6 levels but not with IL-10 or TNF–α. Mol Cell Biochem 397, 97–107 (2014). https://doi.org/10.1007/s11010-014-2176-2

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