The blockade of cytoplasmic HMGB1 modulates the autophagy/apoptosis checkpoint in stressed islet beta cells.
Biochem Biophys Res Commun
; 534: 1053-1058, 2021 01 01.
Article
em En
| MEDLINE
| ID: mdl-33160622
ABSTRACT
High mobility group (HMGB1) is an alarmin known to be harmful to pancreatic beta cells and associated with diabetes mellitus pathogenesis and pancreatic islet graft failure. It has been long thought that the suppression of HMGB1 molecule is beneficial to the beta cells. However, recent studies have indicated that cytoplasmic HMGB1 (cHMGB1) could function as a modulator to relieve cells from apoptotic stress by autophagy induction. Particularly, pancreatic beta cells have been known to utilize the autophagy-to-apoptosis switch when exposed to hypoxia or lipotoxicity. This study aimed to investigate the beta cells under hypoxic and lipotoxic stress while utilizing a small molecule inhibitor of HMGB1, inflachromene (ICM) which can suppress cHMGB1 accumulation. It was revealed that under cellular stress, blockade of cHMGB1 accumulation decreased the viability of islet grafts, primary islets and MIN6 cells. MIN6 cells under cHMGB1 blockade along with lipotoxic stress showed decreased autophagic flux and increased apoptosis. Moreover, cHMGB1 blockade in HFD-fed mice produced unfavorable outcomes on their glucose tolerance. In sum, these results suggested the role of cHMGB1 within beta cell autophagy/apoptosis checkpoint. Given the importance of autophagy in beta cells under apoptotic stresses, this study might provide further insights regarding HMGB1 and diabetes.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína HMGB1
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Células Secretoras de Insulina
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Compostos Heterocíclicos de 4 ou mais Anéis
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2021
Tipo de documento:
Article