Impact of severe hypoglycemia on the heat shock and related protein response.
Adult
Aged
Diabetes Mellitus, Type 2
/ metabolism
Female
HSP70 Heat-Shock Proteins
/ genetics
Heat-Shock Proteins
/ genetics
Heat-Shock Response
Humans
Hypoglycemia
/ metabolism
Interferon-gamma
/ genetics
Interleukins
/ genetics
Intracellular Signaling Peptides and Proteins
/ genetics
Male
Middle Aged
Molecular Chaperones
/ genetics
Protein Serine-Threonine Kinases
/ genetics
Proteome
/ genetics
Receptor, EphA2
/ genetics
Smad3 Protein
/ genetics
Tumor Necrosis Factor-alpha
/ genetics
Ubiquitin-Conjugating Enzymes
/ genetics
Ubiquitin-Protein Ligases
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 08 2021
23 08 2021
Historique:
received:
27
04
2021
accepted:
13
08
2021
entrez:
24
8
2021
pubmed:
25
8
2021
medline:
3
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34426634
doi: 10.1038/s41598-021-96642-8
pii: 10.1038/s41598-021-96642-8
pmc: PMC8382834
doi:
Substances chimiques
EPHA2 protein, human
0
HSP70 Heat-Shock Proteins
0
HSPA1A protein, human
0
HSPB1 protein, human
0
Heat-Shock Proteins
0
Interleukins
0
Intracellular Signaling Peptides and Proteins
0
Molecular Chaperones
0
Proteome
0
SMAD3 protein, human
0
Smad3 Protein
0
Tumor Necrosis Factor-alpha
0
MAP-kinase-activated kinase 5
6YHG2VE3IX
Interferon-gamma
82115-62-6
UBE2G2 protein, human
EC 2.3.2.23
Ubiquitin-Conjugating Enzymes
EC 2.3.2.23
STUB1 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Receptor, EphA2
EC 2.7.10.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Banques de données
ClinicalTrials.gov
['NCT03102801']
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
17057Informations de copyright
© 2021. The Author(s).
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