Association between insulin resistance and impairment of FGF21 signal transduction in skeletal muscles
| Autor: | Hae Jin Kim, Yup Kang, Jong Gab Jung, Ja Young Jeon, Sung-E Choi, Dae Jung Kim, Seung Jin Han, Kwan Woo Lee, Eun Suk Ha, Tae Ho Kim |
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| Rok vydání: | 2014 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty FGF21 Endocrinology Diabetes and Metabolism Muscle Fibers Skeletal 030209 endocrinology & metabolism Biology Impaired glucose tolerance 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology Insulin resistance Lipid oxidation Internal medicine Diabetes mellitus Glucose Intolerance medicine Animals Humans Obesity Phosphorylation Muscle Skeletal Klotho Proteins Glycogen nutritional and metabolic diseases Skeletal muscle Membrane Proteins Lipid metabolism Middle Aged medicine.disease Receptors Fibroblast Growth Factor Diet Fibroblast Growth Factors 030104 developmental biology medicine.anatomical_structure chemistry Diabetes Mellitus Type 2 Insulin Resistance Signal Transduction |
| Zdroj: | Endocrine. 53(1) |
| ISSN: | 1559-0100 |
| Popis: | Fibroblast growth factor (FGF) 21, was identified as a potent metabolic regulator of glucose and lipid metabolism. We investigated whether the levels and signalings of FGF21 changed in the skeletal muscle of type 2 diabetes mellitus (T2DM) patients, participants with impaired glucose tolerance (IGT), human skeletal muscle myotubes (HSMMs) under insulin-resistant conditions, and mice with diet-induced obesity (DIO). A percutaneous biopsy sample of the vastus lateralis muscle of T2DM patients, IGT subjects, and participants with normal glucose tolerance was obtained and the levels and signalings of FGF21 were assessed. We determined whether the expression and signalings of FGF21 in HSMMs altered according to palmitate concentrations and exposure time. Also, we confirmed whether changes of FGF21 signal transduction resulted in the alteration of FGF21 functions. DIO mice were treated intravenously with recombinant FGF21, and the levels and signalings of FGF21 were assessed in their soleus muscles. We checked whether or not FGF21 played a role in the gene transcription related to lipid oxidation. Levels of FGF21 increased, whereas levels of phosphorylated FGF receptor (p-FGFR), phosphorylated FGFR substrates 2α (p-FRS2α), and phosphorylated extracellular signal-regulated kinases (p-ERK) decreased in the skeletal muscle of both T2DM patients and IGT subjects. In vitro, palmitate increased the levels of FGF21 and significantly reduced the levels of β-klotho, p-FGFR, p-FRS2α, and p-ERK1/2 in HSMMs exposed to palmitate. Palmitate also decreased glucose uptake and glycogen contents of FGF21. Consistently, the levels of FGF21 were significantly higher and the levels of β-klotho and p-FGFR were lower in the DIO mice than in normal lean mice. The levels of FGF21 increased but its signal transduction and actions were impaired in skeletal muscles of T2DM patients, IGT subjects, in insulin-resistant HSMMs, and DIO mice. |
| Databáze: | OpenAIRE |
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