Impact of severe hypoglycemia on the heat shock and related protein response
Abstract Heat shock proteins contribute to diabetes-induced complications and are affected by glycemic control. Our hypothesis was that hypoglycemia-induced heat shock and related protein changes would be amplified in type 2 diabetes (T2D). This prospective, case–control study enrolled 23 T2D patien...
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| Format: | Article |
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Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-96642-8 |
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| author | Alexander S. Atkin Abu Saleh Md Moin Manjula Nandakumar Ahmed Al-Qaissi Thozhukat Sathyapalan Stephen L. Atkin Alexandra E. Butler |
| author_facet | Alexander S. Atkin Abu Saleh Md Moin Manjula Nandakumar Ahmed Al-Qaissi Thozhukat Sathyapalan Stephen L. Atkin Alexandra E. Butler |
| author_sort | Alexander S. Atkin |
| collection | DOAJ |
| description | Abstract Heat shock proteins contribute to diabetes-induced complications and are affected by glycemic control. Our hypothesis was that hypoglycemia-induced heat shock and related protein changes would be amplified in type 2 diabetes (T2D). This prospective, case–control study enrolled 23 T2D patients and 23 control subjects who underwent hyperinsulinemic-induced hypoglycemia (≤ 2.0 mmol/L (36 mg/dl)) with blood sampling at baseline, at hypoglycemia and after a 24-h post-hypoglycemia follow-up period. Proteomic analysis of heat shock-related and pro-inflammatory proteins was performed. At baseline, MAPKAPK5 (p = 0.02) and UBE2G2 (p = 0.003) were elevated and STUB1 decreased (p = 0.007) in T2D. At hypoglycemia: PPP3CA (p < 0.03) was increased and EPHA2 (p = 0.01) reduced in T2D; by contrast, three proteins were reduced in controls [HSPA1A (p = 0.007), HSPB1 (p < 0.02), SMAD3 (p = 0.005)] while only MAPKAPK5 was elevated (p = 0.02). In the post-hypoglycemia follow-up period, most proteins normalized to baseline by 24-h; however, STIP1 (p = 0.003), UBE2N (p = 0.004) and UBE2L3 (p < 0.04) were decreased in controls at 24-h. No protein differed from baseline at 24-h in T2D. Pro-inflammatory interleukin-6 increased at 4-h post-hypoglycemia in controls and T2D (p < 0.05 and p < 0.003, respectively) and correlated with HSPA1A; anti-inflammatory IL-10 decreased 2-h post-hypoglycemia in T2D only. Other pro-inflammatory proteins, IL-1α, IFN-γ and TNF-α, were unchanged. Heat shock and related proteins differed at baseline between T2D and controls, with an exaggerated response of heat shock and related proteins to hypoglycemia that returned to baseline, though with changes at 24-h in controls alone. An increase in pro-inflammatory IL-6, with a decrease in anti-inflammatory IL-10, suggests that the HSP system is overactivated due to underlying inflammation in T2D. Trial registration: ClinicalTrials.gov NCT03102801. |
| first_indexed | 2024-12-19T07:07:20Z |
| format | Article |
| id | doaj.art-a5987cfffa694d3688bc0a2df912dfef |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T07:07:20Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
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| spelling | doaj.art-a5987cfffa694d3688bc0a2df912dfef2022-12-21T20:31:15ZengNature PortfolioScientific Reports2045-23222021-08-0111111310.1038/s41598-021-96642-8Impact of severe hypoglycemia on the heat shock and related protein responseAlexander S. Atkin0Abu Saleh Md Moin1Manjula Nandakumar2Ahmed Al-Qaissi3Thozhukat Sathyapalan4Stephen L. Atkin5Alexandra E. Butler6Trinity College, Cambridge UniversityDiabetes Research Center (DRC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF)Diabetes Research Center (DRC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF)Academic Endocrinology, Diabetes and Metabolism, Hull York Medical SchoolAcademic Endocrinology, Diabetes and Metabolism, Hull York Medical SchoolRoyal College of Surgeons of IrelandRoyal College of Surgeons of IrelandAbstract Heat shock proteins contribute to diabetes-induced complications and are affected by glycemic control. Our hypothesis was that hypoglycemia-induced heat shock and related protein changes would be amplified in type 2 diabetes (T2D). This prospective, case–control study enrolled 23 T2D patients and 23 control subjects who underwent hyperinsulinemic-induced hypoglycemia (≤ 2.0 mmol/L (36 mg/dl)) with blood sampling at baseline, at hypoglycemia and after a 24-h post-hypoglycemia follow-up period. Proteomic analysis of heat shock-related and pro-inflammatory proteins was performed. At baseline, MAPKAPK5 (p = 0.02) and UBE2G2 (p = 0.003) were elevated and STUB1 decreased (p = 0.007) in T2D. At hypoglycemia: PPP3CA (p < 0.03) was increased and EPHA2 (p = 0.01) reduced in T2D; by contrast, three proteins were reduced in controls [HSPA1A (p = 0.007), HSPB1 (p < 0.02), SMAD3 (p = 0.005)] while only MAPKAPK5 was elevated (p = 0.02). In the post-hypoglycemia follow-up period, most proteins normalized to baseline by 24-h; however, STIP1 (p = 0.003), UBE2N (p = 0.004) and UBE2L3 (p < 0.04) were decreased in controls at 24-h. No protein differed from baseline at 24-h in T2D. Pro-inflammatory interleukin-6 increased at 4-h post-hypoglycemia in controls and T2D (p < 0.05 and p < 0.003, respectively) and correlated with HSPA1A; anti-inflammatory IL-10 decreased 2-h post-hypoglycemia in T2D only. Other pro-inflammatory proteins, IL-1α, IFN-γ and TNF-α, were unchanged. Heat shock and related proteins differed at baseline between T2D and controls, with an exaggerated response of heat shock and related proteins to hypoglycemia that returned to baseline, though with changes at 24-h in controls alone. An increase in pro-inflammatory IL-6, with a decrease in anti-inflammatory IL-10, suggests that the HSP system is overactivated due to underlying inflammation in T2D. Trial registration: ClinicalTrials.gov NCT03102801.https://doi.org/10.1038/s41598-021-96642-8 |
| spellingShingle | Alexander S. Atkin Abu Saleh Md Moin Manjula Nandakumar Ahmed Al-Qaissi Thozhukat Sathyapalan Stephen L. Atkin Alexandra E. Butler Impact of severe hypoglycemia on the heat shock and related protein response Scientific Reports |
| title | Impact of severe hypoglycemia on the heat shock and related protein response |
| title_full | Impact of severe hypoglycemia on the heat shock and related protein response |
| title_fullStr | Impact of severe hypoglycemia on the heat shock and related protein response |
| title_full_unstemmed | Impact of severe hypoglycemia on the heat shock and related protein response |
| title_short | Impact of severe hypoglycemia on the heat shock and related protein response |
| title_sort | impact of severe hypoglycemia on the heat shock and related protein response |
| url | https://doi.org/10.1038/s41598-021-96642-8 |
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