
Anders Rosengren
Postdoctoral research fellow

Sulforaphane improves disrupted ER-mitochondria interactions and suppresses exaggerated hepatic glucose production
Author
Summary, in English
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 and methods: 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.
Department/s
- Diabetes - Islet Patophysiology
- Genomics, Diabetes and Endocrinology
- EXODIAB: Excellence of Diabetes Research in Sweden
Publishing year
2018
Language
English
Pages
205-214
Publication/Series
Molecular and Cellular Endocrinology
Volume
461
Document type
Journal article
Publisher
Elsevier
Topic
- Endocrinology and Diabetes
Keywords
- Mitochondria-associated ER membranes
- Sulphoraphane
- Type 2 diabetes
Status
Published
Research group
- Diabetes - Islet Patophysiology
- Genomics, Diabetes and Endocrinology
ISBN/ISSN/Other
- ISSN: 0303-7207