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Insulin‐dependent glucose uptake is regulated by mitochondrial Ca 2+ handling in skeletal muscle fibers
Author(s) -
ContrerasFerrat Ariel Eduardo,
DíazVegas Alexis,
Campos Cristian,
Utreras Yildy,
Valladares Denisse,
Rosales Giovanni,
Llanos Paola,
Arias Manuel,
Jaimovich Enrique
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1100.15
Subject(s) - mitochondrion , insulin , glut4 , glucose uptake , medicine , endocrinology , insulin receptor , calcium , inositol , chemistry , biology , receptor , microbiology and biotechnology , insulin resistance
The mitochondria functions rapidly to respond to high energy food supply but the role of mitochondrial Ca 2+ levels in the context of insulin signaling has not been explored. Material and Methods Mice were fed with normal chow diet (NCD) or high fat diet (HFD) for 1 (St‐HFD) or 8 (Lt‐HFD) weeks, (short‐ and long‐term) respectively. Changes in calcium levels, mitochondria membrane potential and glucose uptake were evaluated in living fibers from Flexor digitorum brevis muscle using fluorescent dyes. Results Insulin induced an increase in cytoplasmic and mitochondrial Ca 2+ in adult fibers that was significantly smaller in fibers from short‐term HFD fed mice and completely inhibited in Lt‐HFD. In fibers from NCD fed mice, insulin‐dependent mitochondrial Ca 2+ uptake was blunted by both inositol‐1,4,5‐trisphosphate receptor inhibition and knockdown. The mitochondrial potential was larger in fibers from short‐term HFD fed mice v/s NCD derived fibers and the recruited of active mitochondria was increased. The glucose analogue (2‐NBDG) uptake and the redistribution of GLUT4 myc ‐eGFP chimera induced by insulin were decreased in the absence of mitochondrial Ca 2+ uptake in conditions of type 1inositol 1,4,5‐trisphosphate receptor knockdown. Discussion These effects suggest a role for mitochondrial Ca 2+ uptake in a retrograde regulation of insulin signaling by mitochondria. Support or Funding Information Financed by FONDECYT 11130267, 1151293, PIA‐ACT1111