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VERSION:2.0
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SUMMARY:“Mitochondria-Associated endoplasmic reticulum Membrane (MAM) in
 tegrity is required for insulin signalling and is implicated in hepatic in
 sulin resistance”
DTSTART:20140806T100000
DTEND:20140806T110000
DTSTAMP:20260407T010655Z
UID:47be812beab2a3d73746a62340e7bf38f5467db75ca6b6ec1733b94a
CATEGORIES:Conferences - Seminars
DESCRIPTION:Emily TUBBS\nINSERM U1060\, INRA1397\, Faculté de Médecine L
 yon Sud\, France\n\n	Mitochondria-associated endoplasmic reticulum membran
 es (MAM) are functional domains between both organelles involved in Ca2+ e
 xchange\, through the VDAC1/Grp75/IP3R1 complex\, and regulating energy me
 tabolism. Whereas mitochondrial dysfunction\, ER stress and altered Ca2+ h
 omeostasis are associated with altered insulin signalling\, the implicatio
 n of MAM dysfunctions in insulin resistance is unknown. We validated an ap
 proach based on in situ proximity ligation assay to detect and quantify VD
 AC1/IP3R1 and Grp75/IP3R1 interactions at MAM interface. We demonstrated t
 hat 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 inhibiti
 on of the mitochondrial MAM protein\, cyclophilin D (CypD)\, altered insul
 in signalling in mouse and human primary hepatocytes and treatment of CypD
 -KO mice with metformin improved both insulin sensitivity and MAM integrit
 y. Furthermore\, ER-mitochondria interactions are altered in liver of both
  ob/ob and diet-induced insulin resistant mice\, and improved by rosiglita
 zone treatment in the latter. Finally\, increasing organelle contacts by o
 verexpressing CypD\, enhanced insulin action in primary hepatocytes of dia
 betic mice. Collectively\, our data reveal a new role of MAM integrity in 
 hepatic insulin action and resistance\, providing a novel target for the m
 odulation of insulin action.
LOCATION:AI 1153 https://plan.epfl.ch/?room==AI%201153
STATUS:CANCELLED
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