title: 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.
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.
authors.affiliation: 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.
authors.forename: Mirna Stela
authors.initials: MS
authors.lastname: Ludwig
authors.forename: Vânia Cibele
authors.initials: VC
authors.lastname: Minguetti-Câmara
authors.forename: Thiago Gomes
authors.initials: TG
authors.lastname: Heck
authors.forename: Sofia Pizzato
authors.initials: SP
authors.lastname: Scomazzon
authors.forename: Patrícia Renck
authors.initials: PR
authors.lastname: Nunes
authors.forename: Roberto Barbosa
authors.initials: RB
authors.lastname: Bazotte
authors.forename: Paulo Ivo
authors.initials: PI
authors.lastname: Homem de Bittencourt
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D050884:HSP72 Heat-Shock Proteins / Q000097:blood*; D007003:Hypoglycemia / Q000097:blood* / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000494:pharmacology; D007328:Insulin / Q000009:adverse effects* / Q000494:pharmacology; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D050884:HSP72 Heat-Shock Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
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