Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance
| العنوان: | Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance |
|---|---|
| المؤلفون: | Emily Tubbs, Nadia BENDRIDI, Jennifer Rieusset, Guillaume Vial, Team1 Carmen, Hubert VIDAL, Fabien Zoulim, Team2 Carmen, Birke Bartosch, Carmen Lab, Team3 Carmen, Marie-Agnes BERGER, Jingwei Ji-Cao |
| المساهمون: | Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL) |
| المصدر: | Diabetes Diabetes, American Diabetes Association, 2014, 63 (10), pp.3279-94. ⟨10.2337/db13-1751⟩ |
| بيانات النشر: | HAL CCSD, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Endoplasmic Reticulum, Inbred C57BL, Endoplasmic Reticulum/*metabolism, Mice, 0302 clinical medicine, Insulin, Cells, Cultured, 0303 health sciences, Cultured, biology, Intracellular Membranes/*metabolism, Mitochondria, Liver, Hepatocytes/cytology/metabolism, VDAC1, Signal Transduction, medicine.medical_specialty, Voltage-dependent anion channel, Cells, Insulin/*metabolism, Cell Line, 03 medical and health sciences, Insulin resistance, Internal medicine, Internal Medicine, medicine, Humans, Animals, 030304 developmental biology, Mitochondria/*metabolism, Endoplasmic reticulum membrane, Liver/*metabolism, Signal Transduction/physiology, Endoplasmic reticulum, Intracellular Membranes, medicine.disease, Mice, Inbred C57BL, Insulin receptor, Endocrinology, Insulin Resistance/*physiology, Hepatocytes, biology.protein, Unfolded protein response, Insulin Resistance, 030217 neurology & neurosurgery |
| الوصف: | International audience; Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are functional domains between both organelles involved in Ca(2+) exchange, through the voltage-dependent anion channel (VDAC)-1/glucose-regulated protein 75 (Grp75)/inositol 1,4,5-triphosphate receptor (IP3R)-1 complex, and regulating energy metabolism. Whereas mitochondrial dysfunction, ER stress, and altered Ca(2+) homeostasis are associated with altered insulin signaling, the implication of MAM dysfunctions in insulin resistance is unknown. Here we validated an approach based on in situ proximity ligation assay to detect and quantify VDAC1/IP3R1 and Grp75/IP3R1 interactions at the MAM interface. We demonstrated that MAM integrity is required for insulin signaling and that induction of MAM prevented palmitate-induced alterations of insulin signaling in HuH7 cells. Disruption of MAM integrity by genetic or pharmacological inhibition of the mitochondrial MAM protein, cyclophilin D (CypD), altered insulin signaling in mouse and human primary hepatocytes and treatment of CypD knockout 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. |
| اللغة: | English |
| تدمد: | 0012-1797 |
| DOI: | 10.2337/db13-1751⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d96c419d22e24a898c457921ba793a97 https://hal.archives-ouvertes.fr/hal-01859367 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d96c419d22e24a898c457921ba793a97 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00121797 |
|---|---|
| DOI: | 10.2337/db13-1751⟩ |