Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia

Mild hypoglycemia is common in clinical practice. Severe hypoglycemia results in heat shock protein and associate co-chaperone changes. Whether mild prolonged hypoglycemia elicits a similar response with inflammatory and oxidative-stress responses compared with a severe hypoglycemic event is unclear...

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Autores principales:	Abu Saleh Md Moin, Manjula Nandakumar, Hassan Kahal, Thozhukat Sathyapalan, Stephen L. Atkin, Alexandra E. Butler
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	type 2 diabetes hypoglycemia heat shock proteins oxidative stress inflammatory proteins Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8317ded7de7842c79ac199c7b013c737
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spelling	oai:doaj.org-article:8317ded7de7842c79ac199c7b013c7372021-11-25T17:11:35ZHeat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia10.3390/cells101131092073-4409https://doaj.org/article/8317ded7de7842c79ac199c7b013c7372021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3109https://doaj.org/toc/2073-4409Mild hypoglycemia is common in clinical practice. Severe hypoglycemia results in heat shock protein and associate co-chaperone changes. Whether mild prolonged hypoglycemia elicits a similar response with inflammatory and oxidative-stress responses compared with a severe hypoglycemic event is unclear; therefore, this pilot exploratory study was undertaken. We performed a case–control induced hypoglycemia clamp study, maintaining blood glucose at 2.8 mmol/L (50 mg/dL) for 1 h in 17 subjects (T2D (<i>n</i> = 10); controls (<i>n</i> = 7)). Blood sampling was performed at baseline, hypoglycemia, and 24 h; slow off-rate modified aptamer (SOMA)-scan plasma protein analysis of HSP-related proteins, inflammatory stress markers, and oxidative stress markers was performed. In total, 16 HSPs were analyzed. At baseline, TLR4:MD-2 complex was elevated (<i>p</i> = 0.01), whilst HSPA8 was lower (<i>p</i> < 0.05) in T2D. At hypoglycemia, UBE2N, STIP1, and UBE2L3 increased (all <i>p</i> < 0.05), whilst TLR4:MD-2 and HSPA8 decreased (<i>p</i> < 0.05) in T2D versus baseline. In follow-up after hypoglycemia, HSPs normalized to baseline by 24 h, except UBE2L3 (<i>p</i> < 0.05), which was decreased in controls versus baseline. Correlation of altered inflammatory markers with HSPs revealed the following: at baseline, TLR4:MD-2 correlated with CXCL10 (<i>p</i> < 0.01) and SIGLEC1 (<i>p</i> < 0.05) in controls; HSPA8 negatively correlated with IL5 (<i>p</i> < 0.05) in T2D. A negative correlation between urinary isoprostane 8-iso PGF2α, a marker of oxidative stress, and HSPA1A was seen at 24 h in T2D only (<i>p</i> < 0.05). In conclusion, the HSP changes seen for mild prolonged hypoglycemia were similar to those previously reported for a severe event. However, mild prolonged hypoglycemia appeared to elicit an increased inflammatory response that was associated with heat shock and related proteins.Abu Saleh Md MoinManjula NandakumarHassan KahalThozhukat SathyapalanStephen L. AtkinAlexandra E. ButlerMDPI AGarticletype 2 diabeteshypoglycemiaheat shock proteinsoxidative stressinflammatory proteinsBiology (General)QH301-705.5ENCells, Vol 10, Iss 3109, p 3109 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	type 2 diabetes hypoglycemia heat shock proteins oxidative stress inflammatory proteins Biology (General) QH301-705.5
spellingShingle	type 2 diabetes hypoglycemia heat shock proteins oxidative stress inflammatory proteins Biology (General) QH301-705.5 Abu Saleh Md Moin Manjula Nandakumar Hassan Kahal Thozhukat Sathyapalan Stephen L. Atkin Alexandra E. Butler Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia
description	Mild hypoglycemia is common in clinical practice. Severe hypoglycemia results in heat shock protein and associate co-chaperone changes. Whether mild prolonged hypoglycemia elicits a similar response with inflammatory and oxidative-stress responses compared with a severe hypoglycemic event is unclear; therefore, this pilot exploratory study was undertaken. We performed a case–control induced hypoglycemia clamp study, maintaining blood glucose at 2.8 mmol/L (50 mg/dL) for 1 h in 17 subjects (T2D (<i>n</i> = 10); controls (<i>n</i> = 7)). Blood sampling was performed at baseline, hypoglycemia, and 24 h; slow off-rate modified aptamer (SOMA)-scan plasma protein analysis of HSP-related proteins, inflammatory stress markers, and oxidative stress markers was performed. In total, 16 HSPs were analyzed. At baseline, TLR4:MD-2 complex was elevated (<i>p</i> = 0.01), whilst HSPA8 was lower (<i>p</i> < 0.05) in T2D. At hypoglycemia, UBE2N, STIP1, and UBE2L3 increased (all <i>p</i> < 0.05), whilst TLR4:MD-2 and HSPA8 decreased (<i>p</i> < 0.05) in T2D versus baseline. In follow-up after hypoglycemia, HSPs normalized to baseline by 24 h, except UBE2L3 (<i>p</i> < 0.05), which was decreased in controls versus baseline. Correlation of altered inflammatory markers with HSPs revealed the following: at baseline, TLR4:MD-2 correlated with CXCL10 (<i>p</i> < 0.01) and SIGLEC1 (<i>p</i> < 0.05) in controls; HSPA8 negatively correlated with IL5 (<i>p</i> < 0.05) in T2D. A negative correlation between urinary isoprostane 8-iso PGF2α, a marker of oxidative stress, and HSPA1A was seen at 24 h in T2D only (<i>p</i> < 0.05). In conclusion, the HSP changes seen for mild prolonged hypoglycemia were similar to those previously reported for a severe event. However, mild prolonged hypoglycemia appeared to elicit an increased inflammatory response that was associated with heat shock and related proteins.
format	article
author	Abu Saleh Md Moin Manjula Nandakumar Hassan Kahal Thozhukat Sathyapalan Stephen L. Atkin Alexandra E. Butler
author_facet	Abu Saleh Md Moin Manjula Nandakumar Hassan Kahal Thozhukat Sathyapalan Stephen L. Atkin Alexandra E. Butler
author_sort	Abu Saleh Md Moin
title	Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia
title_short	Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia
title_full	Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia
title_fullStr	Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia
title_full_unstemmed	Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia
title_sort	heat shock-related protein responses and inflammatory protein changes are associated with mild prolonged hypoglycemia
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8317ded7de7842c79ac199c7b013c737
work_keys_str_mv	AT abusalehmdmoin heatshockrelatedproteinresponsesandinflammatoryproteinchangesareassociatedwithmildprolongedhypoglycemia AT manjulanandakumar heatshockrelatedproteinresponsesandinflammatoryproteinchangesareassociatedwithmildprolongedhypoglycemia AT hassankahal heatshockrelatedproteinresponsesandinflammatoryproteinchangesareassociatedwithmildprolongedhypoglycemia AT thozhukatsathyapalan heatshockrelatedproteinresponsesandinflammatoryproteinchangesareassociatedwithmildprolongedhypoglycemia AT stephenlatkin heatshockrelatedproteinresponsesandinflammatoryproteinchangesareassociatedwithmildprolongedhypoglycemia AT alexandraebutler heatshockrelatedproteinresponsesandinflammatoryproteinchangesareassociatedwithmildprolongedhypoglycemia
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Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia

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