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Fibroblast Growth Factor 21 Promotes Glucose Uptake in Adult Skeletal Muscle Fibers from Mice
Author(s) -
RosalesSoto Giovanni,
DíazVegas Alexis,
Llanos Paola,
Jaimovich Enrique,
ContrerasFerrat Ariel
Publication year - 2018
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.2018.32.1_supplement.670.6
Subject(s) - glucose uptake , glut4 , skeletal muscle , endocrinology , medicine , glucose transporter , fgf21 , wortmannin , chemistry , biology , insulin , protein kinase b , biochemistry , fibroblast growth factor , phosphorylation , receptor
Fibroblast growth factor 21 (FGF21) is a pleiotropic peptide hormone that has effects in several organs including skeletal muscle, liver and adipose tissue. FGF21 improves the glucose tolerance test in obese‐insulin resistance mice in vivo and increases the glucose uptake in both primary myotubes and C2C12 myoblasts in vitro . However, the effect of FGF21 on glucose uptake and the cellular mechanism involved in this process in adult skeletal muscle fibers is poorly understood. The aim of this study is to assess the effect of FGF21 on GLUT4‐mediated glucose uptake in isolated skeletal muscle fibers. Material and Methods Male mice were used at 6–8 weeks of age. The effect of FGF21 on GLUT4‐mediated glucose uptake was evaluated in single living fibers from flexor digitorum brevis muscle. To determine the glucose uptake, we used 2‐[N‐(7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)amino]‐2‐deoxy‐D‐glucose (2‐NBDG) (300 μM) a phosphorylable, non‐metabolizable fluorescent glucose analog that has been used to monitor glucose uptake in single living cells. Results FGF21 induces a dose‐response effect, increasing the glucose uptake in isolated muscle fibers. This effect is prevented by the use of either Cytochalasin B (5 μM) or Indinavir (100 μM), both antagonists of GLUT4 activity. The use of PI3K inhibitors such as Wortmannin (100 nM) and LY294002 (50 μM) prevents the FGF21‐dependent glucose uptake. Furthermore, FGF21 does not promote Akt phosphorylation in isolated FDB fibers. In fibers electroporated with the construct encoding GLUT4 myc ‐eGFP chimera and stimulated with FGF21 (100 ng/mL) for 20 min, a strong sarcolemmal GLUT4 presence was detected. Conclusions These results suggest that FGF21 promotes GLUT4‐dependent glucose uptake by a mechanism independent of the serine/threonine kinase Akt phosphorylation. This mechanism could be an important therapeutic target to treatment of insulin resistance and type 2 diabetes. Support or Funding Information Financed by FONDECYT 11130267 (AC‐F), 1151293 (EJ) & 11150243 (PL). CONICYT‐PFCHA/Doctorado Nacional/2017‐21171449 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .