Sulforaphane improves disrupted ER-mitochondria interactions and suppresses exaggerated hepatic glucose production.
Mol Cell Endocrinol
; 461: 205-214, 2018 02 05.
Article
em En
| MEDLINE
| ID: mdl-28923347
ABSTRACT
AIMS:
Exaggerated hepatic glucose production is one of the hallmarks of type 2 diabetes. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound. However, the effects of SFN in hepatocytes are yet unclear. Accumulating evidence points to the close structural contacts between the ER and mitochondria, known as mitochondria-associated ER membranes (MAMs), as important hubs for hepatic metabolism. We wanted to investigate whether SFN could affect hepatic glucose production and MAMs. MATERIALS ANDMETHODS:
We used proximity ligation assays, analysis of ER stress markers and glucose production assays in hepatoma cell lines, primary mouse hepatocytes and diabetic animal models.RESULTS:
SFN counteracted the increase of glucose production in palmitate-treated mouse hepatocytes. SFN also counteracted palmitate-induced MAM disruptions. Moreover, SFN decreased the ER stress markers CHOP and Grp78. In ob/ob mice, SFN improved glucose tolerance and reduced exaggerated glucose production. In livers of these mice, SFN increased MAM protein content, restored impaired VDAC1-IP3R1 interactions and reduced ER stress markers. In mice on HFHSD, SFN improved glucose tolerance, MAM protein content and ER-mitochondria interactions to a similar extent to that of metformin.CONCLUSIONS:
The present findings show that MAMs are severely reduced in animal models of glucose intolerance, which reinforces the role of MAMs as a hub for insulin signaling in the liver. We also show that SFN restores MAMs and improves glucose tolerance by a similar magnitude to that of metformin. These data highlight SFN as a new potential anti-diabetic compound.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Isotiocianatos
/
Retículo Endoplasmático
/
Glucose
/
Fígado
/
Mitocôndrias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article