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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Heat-Shock Response*; Hypoglycemia/*metabolism ; Inflammation/*metabolism ; Proteins/*metabolism; Adult ; Biomarkers/metabolism ; Case-Control Studies ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/metabolism ; Dinoprost/analogs & derivatives ; Dinoprost/metabolism ; Female ; Heat-Shock Proteins/blood ; Humans ; Hypoglycemia/blood ; Male ; Middle Aged ; Oxidative Stress ; Protein Interaction Mapping ; Ubiquitin-Conjugating Enzymes/metabolism

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.

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Keywords: heat shock proteins; hypoglycemia; inflammatory proteins; oxidative stress; type 2 diabetes

ClinicalTrials.gov NCT02205996

0 (Biomarkers)
0 (Heat-Shock Proteins)
0 (Proteins)
27415-26-5 (8-epi-prostaglandin F2alpha)
B7IN85G1HY (Dinoprost)
EC 2.3.2.23 (UBE2L3 protein, human)
EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes)

Date Created: 20211127 Date Completed: 20211215 Latest Revision: 20211215

20250114

PMC8618421

10.3390/cells10113109

34831332