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Sökning: WFRF:(Migliorini Adriana) > Direct Substrate De...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003139naa a2200445 4500
001oai:DiVA.org:uu-318381
003SwePub
008170324s2017 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3183812 URI
0247 a https://doi.org/10.2337/db16-10882 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Kabra, Uma D4 aut
2451 0a Direct Substrate Delivery into Mitochondrial-Fission Deficient Pancreatic Islets Rescues Insulin Secretion
264 c 2017-02-07
264 1b American Diabetes Association,c 2017
338 a print2 rdacarrier
520 a In pancreatic beta cells, mitochondrial bioenergetics control glucose-stimulated insulin secretion (GSIS). Mitochondrial dynamics are generally associated with quality control, maintaining the functionality of bioenergetics. By acute pharmacological inhibition of mitochondrial fission protein Drp1, we here demonstrate that mitochondrial fission is necessary for GSIS in mouse and human islets. We confirm that genetic silencing of Drp1 increases mitochondrial proton leak in MIN6 cells. However, our comprehensive analysis of pancreatic islet bioenergetics reveals that Drp1 does not control insulin secretion via its effect on proton leak but instead via modulation of glucose-fuelled respiration. Notably, pyruvate fully rescues the impaired insulin secretion of fission-deficient beta cells, demonstrating that defective mitochondrial dynamics solely impact substrate supply upstream of oxidative phosphorylation. The present findings provide novel insights in how mitochondrial dysfunction may cause pancreatic beta cell failure. In addition, the results will stimulate new thinking in the intersecting fields of mitochondrial dynamics and bioenergetics, as treatment of defective dynamics in mitochondrial diseases appears to be possible by improving metabolism upstream of mitochondria.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng
7001 a Pfuhlmann, Katrin4 aut
7001 a Migliorini, Adriana4 aut
7001 a Keipert, Susanne4 aut
7001 a Lamp, Daniel4 aut
7001 a Korsgren, Olleu Uppsala universitet,Klinisk immunologi4 aut0 (Swepub:uu)ollekors
7001 a Gegg, Moritz4 aut
7001 a Woods, Stephen C4 aut
7001 a Pfluger, Paul T4 aut
7001 a Lickert, Heiko4 aut
7001 a Affourtit, Charles4 aut
7001 a Tschöp, Matthias H4 aut
7001 a Jastroch, Martin4 aut
7102 a Uppsala universitetb Klinisk immunologi4 org
7730 t Diabetesd : American Diabetes Associationg 66:5, s. 1247-1257q 66:5<1247-1257x 0012-1797x 1939-327X
8564 u https://diabetes.diabetesjournals.org/content/diabetes/66/5/1247.full.pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-318381
8564 8u https://doi.org/10.2337/db16-1088

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