Plasma heat shock protein response to euglycemia in type 2 diabetes

Atkin, Alexander S.; Moin, Abu Saleh; Al-Qaissi, Ahmed; Sathyapalan, Thozhukat; Atkin, Stephen L.; Butler, Alexandra E.

Abstract

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.

Citation

Atkin, A. S., Moin, A. S., Al-Qaissi, A., Sathyapalan, T., Atkin, S. L., & Butler, A. E. (2021). Plasma heat shock protein response to euglycemia in type 2 diabetes. BMJ Open Diabetes Research and Care, 9(1), Article e002057. https://doi.org/10.1136/bmjdrc-2020-002057

• Journal Article Type: Article
• Acceptance Date: Mar 28, 2021
• Online Publication Date: Apr 20, 2021
• Publication Date: Apr 20, 2021
• Deposit Date: May 15, 2021
• Publicly Available Date: May 18, 2021
• Journal: BMJ Open Diabetes Research and Care
• Electronic ISSN: 2052-4897
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 1
• Article Number: e002057
• DOI: https://doi.org/10.1136/bmjdrc-2020-002057
• Public URL: https://hull-repository.worktribe.com/output/3763845