Lowered extracellular pH is involved in the pathogenesis of skeletal muscle insulin resistance
| Autor: | Hiroki Hayata, Naomi Niisato, Noriko Yokoyama, Yoshinori Marunaka, Hiroaki Miyazaki |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Glucose uptake medicine.medical_treatment Blotting Western Muscle Fibers Skeletal Biophysics Deoxyglucose Biochemistry Cell Line Myoblasts Insulin resistance Internal medicine medicine Extracellular Animals Hypoglycemic Agents Insulin Phosphorylation Muscle Skeletal Molecular Biology Protein kinase B biology Cell Membrane Skeletal muscle Cell Differentiation Cell Biology Hydrogen-Ion Concentration medicine.disease Receptor Insulin Rats Insulin receptor Endocrinology medicine.anatomical_structure biology.protein Insulin Resistance Extracellular Space Proto-Oncogene Proteins c-akt |
| Zdroj: | Biochemical and Biophysical Research Communications. 445:170-174 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2014.01.162 |
| Popis: | Insulin resistance in the skeletal muscle is manifested by diminished insulin-stimulated glucose uptake and is a core factor in the pathogenesis of type 2 diabetes mellitus (DM), but the mechanism causing insulin resistance is still unknown. Our recent study has shown that pH of interstitial fluids was lowered in early developmental stage of insulin resistance in OLETF rats, a model of type 2 DM. Therefore, in the present study, we confirmed effects of the extracellular pH on the insulin signaling pathway in a rat skeletal muscle-derived cell line, L6 cell. The phosphorylation level (activation) of the insulin receptor was significantly diminished in low pH media. The phosphorylation level of Akt, which is a downstream target of the insulin signaling pathway, also decreased in low pH media. Moreover, the insulin binding to its receptor was reduced by lowering extracellular pH, while the expression of insulin receptors on the plasma membrane was not affected by the extracellular pH. Finally, insulin-stimulated 2-deoxyglucose uptake in L6 cells was diminished in low pH media. Our present study suggests that lowered extracellular pH conditions may produce the pathogenesis of insulin resistance in skeletal muscle cells. |
| Databáze: | OpenAIRE |
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