Activation of Imidazoline I-2B Receptor by Metformin to Increase Glucose Uptake in Skeletal Muscle
| Autor: | Juei-Tang Cheng, Kai-Chun Cheng, Ching Hua Yeh, C. T. Chen, Hsien-Hui Chung, Wency Chen |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty endocrine system diseases Endocrinology Diabetes and Metabolism Glucose uptake Clinical Biochemistry AMP-Activated Protein Kinases Carbohydrate metabolism Biochemistry Cell Line Phosphatidylinositol 3-Kinases Endocrinology AMP-activated protein kinase Internal medicine Diabetes mellitus medicine Animals Phosphorylation Rats Wistar Muscle Skeletal Protein Kinase C biology Chemistry Biochemistry (medical) Imidazoles Glucose transporter nutritional and metabolic diseases Skeletal muscle AMPK General Medicine medicine.disease Metformin Rats Glucose medicine.anatomical_structure biology.protein Imidazoline Receptors Signal Transduction medicine.drug |
| Zdroj: | Hormone and Metabolic Research. 43:708-713 |
| ISSN: | 1439-4286 0018-5043 |
| DOI: | 10.1055/s-0031-1286259 |
| Popis: | Metformin (dimethylbiguanide) belongs to guanidinium-derivative and is widely used for treatment of diabetic disorders in clinic. Metformin lowers blood glucose in diabetic animals through increase of glucose uptake into skeletal muscle. Recent evidence indicates that activation of imidazoline I2B receptor (I2BR) by guanidinium-derivatives also increased glucose uptake; however, the effect of metformin on I2BR is still unknown. The blood glucose levels were determined by a glucose kit. The ability of glucose uptake into isolated skeletal muscle or cultured C2C12 cells was determined using 2-[14C]-deoxyglucose as tracer. The expressions of 5' AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT-4) were identified by Western blotting analysis. The metformin-induced blood glucose-lowering action was dose-dependently blocked by BU224, a specific I2R antagonist, in Wistar rats. Also, similar reversion by BU224 was observed in isolated skeletal muscle regarding the metformin-induced glucose uptake. Moreover, AMPK phosphorylation by metformin was concentration-dependently reduced by BU224 in isolated skeletal muscle. In addition, signals for metformin increased glucose uptake were identified via I2R/PI3K/PKC/AMPK dependent pathway in C2C12 cells. Thus, we suggest that metformin can activate I2BR to increase glucose uptake and I2BR will be a new target for diabetic therapy. |
| Databáze: | OpenAIRE |
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