Plasma heat shock protein response to euglycemia in type 2 diabetes
Introduction Glucose variability is associated with mortality and macrovascular diabetes complications. The mechanisms through which glucose variability mediates tissue damage are not well understood, although cellular oxidative stress is likely involved. As heat shock proteins (HSPs) play a role in...
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BMJ Publishing Group
2021-03-01
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| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/9/1/e002057.full |
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| author | Stephen L Atkin Thozhukat Sathyapalan Alexandra E Butler Abu Saleh Md Moin Alexander S Atkin Ahmed Al-Qaissi |
| author_facet | Stephen L Atkin Thozhukat Sathyapalan Alexandra E Butler Abu Saleh Md Moin Alexander S Atkin Ahmed Al-Qaissi |
| author_sort | Stephen L Atkin |
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| description | Introduction Glucose variability is associated with mortality and macrovascular diabetes complications. The mechanisms through which glucose variability mediates tissue damage are not well understood, although cellular oxidative stress is likely involved. As heat shock proteins (HSPs) play a role in the pathogenesis of type 2 diabetes (T2D) complications and are rapidly responsive, we hypothesized that HSP-related proteins (HSPRPs) would differ in diabetes and may respond to glucose normalization.Research design and methods A prospective, parallel study in T2D (n=23) and controls (n=23) was undertaken. T2D subjects underwent insulin-induced blood glucose normalization from baseline 7.6±0.4 mmol/L (136.8±7.2 mg/dL) to 4.5±0.07 mmol/L (81±1.2 mg/dL) for 1 hour. Control subjects were maintained at 4.9±0.1 mmol/L (88.2±1.8 mg/dL). Slow Off-rate Modified Aptamer-scan plasma protein measurement determined a panel of HSPRPs.Results At baseline, E3-ubiquitin-protein ligase (carboxyl-terminus of Hsc70 interacting protein (CHIP) or HSPABP2) was lower (p=0.03) and ubiquitin-conjugating enzyme E2G2 higher (p=0.003) in T2D versus controls. Following glucose normalization, DnaJ homolog subfamily B member 1 (DNAJB1 or HSP40) was reduced (p=0.02) in T2D, with HSP beta-1 (HSPB1) and HSP-70-1A (HSP70-1A) (p=0.07 and p=0.09, respectively) also approaching significance relative to T2D baseline levels.Conclusions Key HSPRPs involved in critical protein interactions, CHIP and UBE2G2, were altered in diabetes at baseline. DNAJB1 fell in response to euglycemia, suggesting that HSPs are reacting to basal stress that could be mitigated by tight glucose control with reduction of glucose variability. |
| format | Article |
| id | doaj-art-5327b2e1d0474c689d3a667848a39331 |
| institution | Kabale University |
| issn | 2052-4897 |
| language | English |
| publishDate | 2021-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Diabetes Research & Care |
| spelling | doaj-art-5327b2e1d0474c689d3a667848a393312024-12-12T07:30:14ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972021-03-019110.1136/bmjdrc-2020-002057Plasma heat shock protein response to euglycemia in type 2 diabetesStephen L Atkin0Thozhukat Sathyapalan1Alexandra E Butler2Abu Saleh Md Moin3Alexander S Atkin4Ahmed Al-Qaissi5Royal College of Surgeons in Ireland and Medical University of Bahrain, Busaiteen, BahrainDiabetes and Endocrinology, Hull University Teaching Hospitals NHS Trust, Hull, UKDiabetes Research Center (DRC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (Q.F.), Doha, QatarDiabetes Research Center, Qatar Biomedical Research Institute, Doha, QatarDepartment of Biochemistry, University of Cambridge, Cambridgeshire, UKDiabetes and Metabolism, Hull York Medical School, Hull, UKIntroduction Glucose variability is associated with mortality and macrovascular diabetes complications. The mechanisms through which glucose variability mediates tissue damage are not well understood, although cellular oxidative stress is likely involved. As heat shock proteins (HSPs) play a role in the pathogenesis of type 2 diabetes (T2D) complications and are rapidly responsive, we hypothesized that HSP-related proteins (HSPRPs) would differ in diabetes and may respond to glucose normalization.Research design and methods A prospective, parallel study in T2D (n=23) and controls (n=23) was undertaken. T2D subjects underwent insulin-induced blood glucose normalization from baseline 7.6±0.4 mmol/L (136.8±7.2 mg/dL) to 4.5±0.07 mmol/L (81±1.2 mg/dL) for 1 hour. Control subjects were maintained at 4.9±0.1 mmol/L (88.2±1.8 mg/dL). Slow Off-rate Modified Aptamer-scan plasma protein measurement determined a panel of HSPRPs.Results At baseline, E3-ubiquitin-protein ligase (carboxyl-terminus of Hsc70 interacting protein (CHIP) or HSPABP2) was lower (p=0.03) and ubiquitin-conjugating enzyme E2G2 higher (p=0.003) in T2D versus controls. Following glucose normalization, DnaJ homolog subfamily B member 1 (DNAJB1 or HSP40) was reduced (p=0.02) in T2D, with HSP beta-1 (HSPB1) and HSP-70-1A (HSP70-1A) (p=0.07 and p=0.09, respectively) also approaching significance relative to T2D baseline levels.Conclusions Key HSPRPs involved in critical protein interactions, CHIP and UBE2G2, were altered in diabetes at baseline. DNAJB1 fell in response to euglycemia, suggesting that HSPs are reacting to basal stress that could be mitigated by tight glucose control with reduction of glucose variability.https://drc.bmj.com/content/9/1/e002057.full |
| spellingShingle | Stephen L Atkin Thozhukat Sathyapalan Alexandra E Butler Abu Saleh Md Moin Alexander S Atkin Ahmed Al-Qaissi Plasma heat shock protein response to euglycemia in type 2 diabetes BMJ Open Diabetes Research & Care |
| title | Plasma heat shock protein response to euglycemia in type 2 diabetes |
| title_full | Plasma heat shock protein response to euglycemia in type 2 diabetes |
| title_fullStr | Plasma heat shock protein response to euglycemia in type 2 diabetes |
| title_full_unstemmed | Plasma heat shock protein response to euglycemia in type 2 diabetes |
| title_short | Plasma heat shock protein response to euglycemia in type 2 diabetes |
| title_sort | plasma heat shock protein response to euglycemia in type 2 diabetes |
| url | https://drc.bmj.com/content/9/1/e002057.full |
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