Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes
Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter. AICAR is an intermediate in the purine de novo synthesis, and its tissue conc...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | Journal of Nutrition and Metabolism |
| Online Access: | http://dx.doi.org/10.1155/2012/132056 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849404595978108928 |
|---|---|
| author | Giuseppina T. Russo Letteria Minutoli Alessandra Bitto Domenica Altavilla Eugenio Alessi Annalisa Giandalia Elisabetta L. Romeo Maria Francesca Stagno Francesco Squadrito Domenico Cucinotta Jacob Selhub |
| author_facet | Giuseppina T. Russo Letteria Minutoli Alessandra Bitto Domenica Altavilla Eugenio Alessi Annalisa Giandalia Elisabetta L. Romeo Maria Francesca Stagno Francesco Squadrito Domenico Cucinotta Jacob Selhub |
| author_sort | Giuseppina T. Russo |
| collection | DOAJ |
| description | Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter. AICAR is an intermediate in the purine de novo synthesis, and its tissue concentrations can be increased, in vivo, by low doses of methotrexate (MTX) through the inhibition of the enzyme AICAR transformylase.
We report here the first evidence that, in experimental type 2 diabetes, chronic treatment with low doses of MTX increases skeletal muscle GLUT4 expression and improves metabolic control.
MTX (0.5 mg/kg body weight) or vehicle was administered intraperitoneally, once a week for 4 weeks, to genetically diabetic female C57BL/KsJ-m+/+Leptdb mice (db+/db+) and their normoglycemic littermates (db+/+m).
In the
db+/db+ mice, MTX treatment was associated with a ∼2-fold increase in skeletal muscle GLUT4 protein concentration and a >4-fold increase in GLUT4 mRNA expression (P<0.01, all), as compared to vehicle-treated mice; no significant differences were noted in controls. MTX treatment was also associated with a significant reduction of glucose and insulin serum concentrations in diabetic mice (P<0.001), and glucose levels only (P<0.05) in controls.
These data indicate a different route to increase skeletal muscle GLUT4 expression, through the potential inhibition of the enzyme AICAR transformylase. |
| format | Article |
| id | doaj-art-9b45a9b7b29a4b538da39f59c14faef5 |
| institution | Kabale University |
| issn | 2090-0724 2090-0732 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Nutrition and Metabolism |
| spelling | doaj-art-9b45a9b7b29a4b538da39f59c14faef52025-08-20T03:36:57ZengWileyJournal of Nutrition and Metabolism2090-07242090-07322012-01-01201210.1155/2012/132056132056Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental DiabetesGiuseppina T. Russo0Letteria Minutoli1Alessandra Bitto2Domenica Altavilla3Eugenio Alessi4Annalisa Giandalia5Elisabetta L. Romeo6Maria Francesca Stagno7Francesco Squadrito8Domenico Cucinotta9Jacob Selhub10Department of Internal Medicine, University of Messina, 98122 Messina, ItalySection of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, 98122 Messina, ItalySection of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, 98122 Messina, ItalySection of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, 98122 Messina, ItalyDepartment of Internal Medicine, University of Messina, 98122 Messina, ItalyDepartment of Internal Medicine, University of Messina, 98122 Messina, ItalyDepartment of Internal Medicine, University of Messina, 98122 Messina, ItalyDepartment of Internal Medicine, University of Messina, 98122 Messina, ItalySection of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, 98122 Messina, ItalyDepartment of Internal Medicine, University of Messina, 98122 Messina, ItalyVitamin Bioavailability Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USALong-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter. AICAR is an intermediate in the purine de novo synthesis, and its tissue concentrations can be increased, in vivo, by low doses of methotrexate (MTX) through the inhibition of the enzyme AICAR transformylase. We report here the first evidence that, in experimental type 2 diabetes, chronic treatment with low doses of MTX increases skeletal muscle GLUT4 expression and improves metabolic control. MTX (0.5 mg/kg body weight) or vehicle was administered intraperitoneally, once a week for 4 weeks, to genetically diabetic female C57BL/KsJ-m+/+Leptdb mice (db+/db+) and their normoglycemic littermates (db+/+m). In the db+/db+ mice, MTX treatment was associated with a ∼2-fold increase in skeletal muscle GLUT4 protein concentration and a >4-fold increase in GLUT4 mRNA expression (P<0.01, all), as compared to vehicle-treated mice; no significant differences were noted in controls. MTX treatment was also associated with a significant reduction of glucose and insulin serum concentrations in diabetic mice (P<0.001), and glucose levels only (P<0.05) in controls. These data indicate a different route to increase skeletal muscle GLUT4 expression, through the potential inhibition of the enzyme AICAR transformylase.http://dx.doi.org/10.1155/2012/132056 |
| spellingShingle | Giuseppina T. Russo Letteria Minutoli Alessandra Bitto Domenica Altavilla Eugenio Alessi Annalisa Giandalia Elisabetta L. Romeo Maria Francesca Stagno Francesco Squadrito Domenico Cucinotta Jacob Selhub Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes Journal of Nutrition and Metabolism |
| title | Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes |
| title_full | Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes |
| title_fullStr | Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes |
| title_full_unstemmed | Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes |
| title_short | Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes |
| title_sort | methotrexate increases skeletal muscle glut4 expression and improves metabolic control in experimental diabetes |
| url | http://dx.doi.org/10.1155/2012/132056 |
| work_keys_str_mv | AT giuseppinatrusso methotrexateincreasesskeletalmuscleglut4expressionandimprovesmetaboliccontrolinexperimentaldiabetes AT letteriaminutoli methotrexateincreasesskeletalmuscleglut4expressionandimprovesmetaboliccontrolinexperimentaldiabetes AT alessandrabitto methotrexateincreasesskeletalmuscleglut4expressionandimprovesmetaboliccontrolinexperimentaldiabetes AT domenicaaltavilla methotrexateincreasesskeletalmuscleglut4expressionandimprovesmetaboliccontrolinexperimentaldiabetes AT eugenioalessi methotrexateincreasesskeletalmuscleglut4expressionandimprovesmetaboliccontrolinexperimentaldiabetes AT annalisagiandalia methotrexateincreasesskeletalmuscleglut4expressionandimprovesmetaboliccontrolinexperimentaldiabetes AT elisabettalromeo methotrexateincreasesskeletalmuscleglut4expressionandimprovesmetaboliccontrolinexperimentaldiabetes AT mariafrancescastagno methotrexateincreasesskeletalmuscleglut4expressionandimprovesmetaboliccontrolinexperimentaldiabetes AT francescosquadrito methotrexateincreasesskeletalmuscleglut4expressionandimprovesmetaboliccontrolinexperimentaldiabetes AT domenicocucinotta methotrexateincreasesskeletalmuscleglut4expressionandimprovesmetaboliccontrolinexperimentaldiabetes AT jacobselhub methotrexateincreasesskeletalmuscleglut4expressionandimprovesmetaboliccontrolinexperimentaldiabetes |