“Mitochondria-Associated endoplasmic reticulum Membrane (MAM) integrity is required for insulin signalling and is implicated in hepatic insulin resistance”
Cancelled
Event details
| Date | 06.08.2014 |
| Hour | 10:00 › 11:00 |
| Speaker |
Emily TUBBS INSERM U1060, INRA1397, Faculté de Médecine Lyon Sud, France |
| Location | |
| Category | Conferences - Seminars |
Mitochondria-associated endoplasmic reticulum membranes (MAM) are functional domains between both organelles involved in Ca2+ exchange, through the VDAC1/Grp75/IP3R1 complex, and regulating energy metabolism. Whereas mitochondrial dysfunction, ER stress and altered Ca2+ homeostasis are associated with altered insulin signalling, the implication of MAM dysfunctions in insulin resistance is unknown. We validated an approach based on in situ proximity ligation assay to detect and quantify VDAC1/IP3R1 and Grp75/IP3R1 interactions at MAM interface. We demonstrated that MAM integrity is required for insulin signalling and that induction of MAM prevented palmitate-induced alterations of insulin signalling in HuH7 cells. Disruption of MAM integrity by genetic or pharmacological inhibition of the mitochondrial MAM protein, cyclophilin D (CypD), altered insulin signalling in mouse and human primary hepatocytes and treatment of CypD-KO mice with metformin improved both insulin sensitivity and MAM integrity. Furthermore, ER-mitochondria interactions are altered in liver of both ob/ob and diet-induced insulin resistant mice, and improved by rosiglitazone treatment in the latter. Finally, increasing organelle contacts by overexpressing CypD, enhanced insulin action in primary hepatocytes of diabetic mice. Collectively, our data reveal a new role of MAM integrity in hepatic insulin action and resistance, providing a novel target for the modulation of insulin action.
Practical information
- Informed public
- Free
Organizer
- Kristina Schoonjans and Johan Auwerx for the LIMNA Alliance
Contact
- Kristina Schoonjans and Johan Auwerx
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