Orally Administered Leucine Enhances Protein Synthesis in Skeletal Muscle of Diabetic Rats in the Absence of Increases in 4E-BP1 or S6K1 Phosphorylation
| العنوان: | Orally Administered Leucine Enhances Protein Synthesis in Skeletal Muscle of Diabetic Rats in the Absence of Increases in 4E-BP1 or S6K1 Phosphorylation |
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| المؤلفون: | Joshua C. Anthony, David A. MacLean, Charles H. Lang, Tracy G. Anthony, Stephen J. Crozier, Ali K. Reiter, Scot R. Kimball, Leonard S. Jefferson |
| المصدر: | Diabetes. 51:928-936 |
| بيانات النشر: | American Diabetes Association, 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Blood Glucose, Male, Ribosomal Proteins, medicine.medical_specialty, Phenylalanine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Administration, Oral, Muscle Proteins, P70-S6 Kinase 1, Biology, environment and public health, Diabetes Mellitus, Experimental, Rats, Sprague-Dawley, Leucine, Reference Values, Eukaryotic initiation factor, Internal medicine, Internal Medicine, medicine, Animals, Insulin, Phosphorylation, Infusions, Intravenous, Muscle, Skeletal, Kinase, Ribosomal Protein S6 Kinases, Intracellular Signaling Peptides and Proteins, Skeletal muscle, Phosphoproteins, Rats, Repressor Proteins, Endocrinology, medicine.anatomical_structure, Protein Biosynthesis, Ribosomal protein s6, Carrier Proteins, Food Deprivation |
| الوصف: | In this study, food-deprived (18 h) control rats and rats with alloxan-induced diabetes were orally administered saline or the amino acid leucine to assess whether it regulates protein synthesis independently of a change in serum insulin concentrations. Immediately after leucine administration, diabetic rats were infused with insulin (0.0, 4.0, or 20 pmol small middle dot min(-1) small middle dot kg(-1)) for 1 h to examine the role of the hormone in the protein synthetic response to leucine. In control rats, leucine stimulated protein synthesis by 58% and increased phosphorylation of the translational repressor, eukaryotic initiation factor (eIF) 4E-binding protein (BP)-1, 4E-BP1, fivefold. Consequently, association of the mRNA cap-binding protein eukaryotic initiation factor (eIF)4E with 4E-BP1 was reduced to 50% of control values, and eIF4G*eIF4E complex assembly was increased 80%. Furthermore, leucine increased the phosphorylation of the 70-kDa ribosomal protein S6 (rp S6) and the ribosomal protein S6 kinase (S6K1). Diabetes attenuated protein synthesis compared with control rats. Nonetheless, in diabetic rats, leucine increased protein synthesis by 53% without concomitant changes in the phosphorylation of 4E-BP1 or S6K1. Skeletal muscle protein synthesis was stimulated in diabetic rats infused with insulin, but rates of synthesis remained less than values in nondiabetic controls that were administered leucine. Phosphorylation of 4E-BP1 and S6K1 was increased in diabetic rats infused with insulin in a dose-dependent manner, and the response was enhanced by leucine. The results suggest that leucine enhances protein synthesis in skeletal muscle through both insulin-dependent and -independent mechanisms. The insulin-dependent mechanism is associated with increased phosphorylation of 4E-BP1 and S6K1. In contrast, the insulin-independent effect on protein synthesis is mediated by an unknown mechanism. |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4eab2b375050389de625308c2496422aTest https://doi.org/10.2337/diabetes.51.4.928Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4eab2b375050389de625308c2496422a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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