کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5509464 1538515 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Kalirin, a GEF for Rac1, plays an important role in FSTL-1-mediated glucose uptake in skeletal muscle cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Kalirin, a GEF for Rac1, plays an important role in FSTL-1-mediated glucose uptake in skeletal muscle cells
چکیده انگلیسی


- Myokine, FSTL-1, increases AMPK phosphorylation in skeletal muscle cells.
- FSTL-1 stimulates glucose uptake AMPK dependently.
- Kalirin, GEF for Rac1, is involved in FSTL-1-mediated glucose uptake.
- FSTL-1 becomes therapeutically promising target for the development of treatment drug for diabetes.

Follistatin-like 1 (FSTL-1) is a novel myokine; however, little is known about its metabolic role. Here, FSTL-1 stimulated glucose uptake in an AMP-activated protein kinase (AMPK)-dependent manner in L6 rat skeletal muscle cells. FSTL-1 increased intracellular calcium concentration. Calcium/calmodulin-dependent protein kinase kinase (CaMKK) inhibition blocked FSTL-1-induced AMPK phosphorylation and glucose uptake. In addition, FSTL-1 stimulated the phosphorylation of p21-activated kinase 1 (PAK1), a small GTPase Rac1 downstream protein. PAK1 knockdown or inhibition of Rac1 blocked FSTL-1-induced glucose uptake; moreover, kalirin, a Rac1 guanine nucleotide exchange factor (GEF), was induced by FSTL-1. Kalirin knockdown with siRNA blocked FSTL-1-induced PAK1 phosphorylation and glucose uptake. Consistent with the induction of Rac1 GEF kalirin, the GTP-bound form of Rac1 was increased by FSTL-1. FSTL-1 increased the production of glucose transporter type 4 (GLUT4) protein and also stimulated the translocation of GLUT4 to the plasma membrane. Translocation of GLUT4 was not observed in cells pre-treated with AMPK inhibitor, Rac1 inhibitor, or kalirin siRNA. In primary myoblast cell culture, FSTL-1 increased glucose uptake in an AMPK-dependent manner. A CaMKK inhibitor or kalirin knockdown blocked FSTL-1-induced glucose uptake. These results suggest that kalirin and Rac1 GEF play important roles in FSTL-1-mediated glucose regulation in skeletal muscle cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 29, January 2017, Pages 150-157
نویسندگان
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