Preventing the calorie restriction-induced increase in insulin-stimulated Akt2 phosphorylation eliminates calorie restriction's effect on glucose uptake in skeletal muscle
| Autor: | Donel A. Sequea, Edward B. Arias, Naveen Sharma, Gregory D. Cartee |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Glucose transport Glucose uptake Filamins Calorie restriction Biology Article Insulin resistance Contractile Proteins Internal medicine medicine Animals Insulin Phosphorylation Muscle Skeletal Protein kinase B Molecular Biology Caloric Restriction Microfilament Proteins Glucose transporter Skeletal muscle medicine.disease Insulin sensitivity Receptor Insulin Rats Endocrinology medicine.anatomical_structure Glucose biology.protein Molecular Medicine GLUT4 Heterocyclic Compounds 3-Ring Proto-Oncogene Proteins c-akt hormones hormone substitutes and hormone antagonists |
| Zdroj: | Biochimica et biophysica acta. 1822(11) |
| ISSN: | 0006-3002 |
| Popis: | Calorie restriction (CR; ~60% of ad libitum, AL, consumption) improves insulin-stimulated glucose uptake in skeletal muscle. The precise cellular mechanism for this healthful outcome is unknown, but it is accompanied by enhanced insulin-stimulated activation of Akt. Previous research using Akt2-null mice demonstrated that Akt2 is essential for the full CR-effect on insulin-stimulated glucose uptake by muscle. However, because Akt2-null mice were completely deficient in Akt2 in every cell throughout life, it would be valuable to assess the efficacy of transient, muscle-specific Akt inhibition for attenuation of CR-effects on glucose uptake. Accordingly, we used a selective Akt inhibitor (MK-2206) to eliminate the CR-induced elevation in insulin-stimulated Akt2 phosphorylation and determined the effects on Akt substrates and glucose uptake. We incubated isolated epitrochlearis muscles from 9-month-old AL and CR (~60–65% of AL intake for 6months) rats with or without MK-2206 and measured insulin-stimulated (1.2nM) glucose uptake and phosphorylation of the insulin receptor (Tyr1162/1163), pan-Akt (Thr308 and Ser473), Akt2 (Thr308 and Ser473), AS160/TBC1D4 (Thr642), and Filamin C (Ser2213). Incubation of isolated skeletal muscles with a dose of a selective Akt inhibitor that eliminated the CR-induced increases in Akt2 phosphorylation prevented CR's effects on insulin-stimulated glucose uptake, pAS160Thr642 and pFilamin CSer2213 without altering pIRTyr1162/1163. These data provide compelling new evidence linking the CR-induced increase in insulin-stimulated Akt2 phosphorylation to CR's effects on insulin-mediated phosphorylation of Akt substrates and glucose uptake in skeletal muscle. |
| Databáze: | OpenAIRE |
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