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

<div><p>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 hypoglyce...

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Main Author: Abu Saleh Md Moin (6189512) (author)
Other Authors: Manjula Nandakumar (1545811) (author), Hassan Kahal (9999461) (author), Thozhukat Sathyapalan (704787) (author), Stephen L. Atkin (6684368) (author), Alexandra E. Butler (6189536) (author)
Published: 2021
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_version_ 1864513516739756032
author Abu Saleh Md Moin (6189512)
author2 Manjula Nandakumar (1545811)
Hassan Kahal (9999461)
Thozhukat Sathyapalan (704787)
Stephen L. Atkin (6684368)
Alexandra E. Butler (6189536)
author2_role author
author
author
author
author
author_facet Abu Saleh Md Moin (6189512)
Manjula Nandakumar (1545811)
Hassan Kahal (9999461)
Thozhukat Sathyapalan (704787)
Stephen L. Atkin (6684368)
Alexandra E. Butler (6189536)
author_role author
dc.creator.none.fl_str_mv Abu Saleh Md Moin (6189512)
Manjula Nandakumar (1545811)
Hassan Kahal (9999461)
Thozhukat Sathyapalan (704787)
Stephen L. Atkin (6684368)
Alexandra E. Butler (6189536)
dc.date.none.fl_str_mv 2021-11-10T03:00:00Z
dc.identifier.none.fl_str_mv 10.3390/cells10113109
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Heat_Shock-Related_Protein_Responses_and_Inflammatory_Protein_Changes_Are_Associated_with_Mild_Prolonged_Hypoglycemia/25764339
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Clinical sciences
type 2 diabetes
hypoglycemia
heat shock proteins
oxidative stress
inflammatory proteins
dc.title.none.fl_str_mv Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>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 (n = 10); controls (n = 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 (p = 0.01), whilst HSPA8 was lower (p < 0.05) in T2D. At hypoglycemia, UBE2N, STIP1, and UBE2L3 increased (all p < 0.05), whilst TLR4:MD-2 and HSPA8 decreased (p < 0.05) in T2D versus baseline. In follow-up after hypoglycemia, HSPs normalized to baseline by 24 h, except UBE2L3 (p < 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 (p < 0.01) and SIGLEC1 (p < 0.05) in controls; HSPA8 negatively correlated with IL5 (p < 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 (p < 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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Cells<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/cells10113109" target="_blank">https://dx.doi.org/10.3390/cells10113109</a></p>
eu_rights_str_mv openAccess
id Manara2_825214162760112cebbad8e533a74a92
identifier_str_mv 10.3390/cells10113109
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25764339
publishDate 2021
repository.mail.fl_str_mv
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rights_invalid_str_mv CC BY 4.0
spelling Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged HypoglycemiaAbu Saleh Md Moin (6189512)Manjula Nandakumar (1545811)Hassan Kahal (9999461)Thozhukat Sathyapalan (704787)Stephen L. Atkin (6684368)Alexandra E. Butler (6189536)Biomedical and clinical sciencesClinical sciencestype 2 diabeteshypoglycemiaheat shock proteinsoxidative stressinflammatory proteins<div><p>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 (n = 10); controls (n = 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 (p = 0.01), whilst HSPA8 was lower (p < 0.05) in T2D. At hypoglycemia, UBE2N, STIP1, and UBE2L3 increased (all p < 0.05), whilst TLR4:MD-2 and HSPA8 decreased (p < 0.05) in T2D versus baseline. In follow-up after hypoglycemia, HSPs normalized to baseline by 24 h, except UBE2L3 (p < 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 (p < 0.01) and SIGLEC1 (p < 0.05) in controls; HSPA8 negatively correlated with IL5 (p < 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 (p < 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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Cells<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/cells10113109" target="_blank">https://dx.doi.org/10.3390/cells10113109</a></p>2021-11-10T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/cells10113109https://figshare.com/articles/journal_contribution/Heat_Shock-Related_Protein_Responses_and_Inflammatory_Protein_Changes_Are_Associated_with_Mild_Prolonged_Hypoglycemia/25764339CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/257643392021-11-10T03:00:00Z
spellingShingle Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia
Abu Saleh Md Moin (6189512)
Biomedical and clinical sciences
Clinical sciences
type 2 diabetes
hypoglycemia
heat shock proteins
oxidative stress
inflammatory proteins
status_str publishedVersion
title 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_short 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
topic Biomedical and clinical sciences
Clinical sciences
type 2 diabetes
hypoglycemia
heat shock proteins
oxidative stress
inflammatory proteins