title: Glutamine supplementation stimulates protein-synthetic and inhibits protein-degradative signaling pathways in skeletal muscle of diabetic rats.
abstract: In this study, we investigated the effect of glutamine (Gln) supplementation on the signaling pathways regulating protein synthesis and protein degradation in the skeletal muscle of rats with streptozotocin (STZ)-induced diabetes. The expression levels of key regulatory proteins in the synthetic pathways (Akt, mTOR, GSK3 and 4E-BP1) and the degradation pathways (MuRF-1 and MAFbx) were determined using real-time PCR and Western blotting in four groups of male Wistar rats; 1) control, non-supplemented with glutamine; 2) control, supplemented with glutamine; 3) diabetic, non-supplemented with glutamine; and 4) diabetic, supplemented with glutamine. Diabetes was induced by the intravenous injection of 65 mg/kg bw STZ in citrate buffer (pH 4.2); the non-diabetic controls received only citrate buffer. After 48 hours, diabetes was confirmed in the STZ-treated animals by the determination of blood glucose levels above 200 mg/dL. Starting on that day, a solution of 1 g/kg bw Gln in phosphate buffered saline (PBS) was administered daily via gavage for 15 days to groups 2 and 4. Groups 1 and 3 received only PBS for the same duration. The rats were euthanized, and the soleus muscles were removed and homogenized in extraction buffer for the subsequent measurement of protein and mRNA levels. The results demonstrated a significant decrease in the muscle Gln content in the diabetic rats, and this level increased toward the control value in the diabetic rats receiving Gln. In addition, the diabetic rats exhibited a reduced mRNA expression of regulatory proteins in the protein synthesis pathway and increased expression of those associated with protein degradation. A reduction in the skeletal muscle mass in the diabetic rats was observed and was alleviated partially with Gln supplementation. The data suggest that glutamine supplementation is potentially useful for slowing the progression of muscle atrophy in patients with diabetes.
authors.affiliation: Institute of Physical Activity Sciences and Sports, Post-Graduate Program in Human Movement Sciences, Cruzeiro do Sul University, São Paulo, Brazil.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Lambertucci
authors.forename: Rafael H
authors.initials: RH
authors.lastname: Lambertucci
authors.forename: Sandro M
authors.initials: SM
authors.lastname: Hirabara
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.forename: Anselmo S
authors.initials: AS
authors.lastname: Moriscot
authors.forename: Tatiana C
authors.initials: TC
authors.lastname: Alba-Loureiro
authors.forename: Lucas
authors.initials: L
authors.lastname: Guimarães-Ferreira
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Levada-Pires
authors.forename: Diogo A A
authors.initials: DA
authors.lastname: Vasconcelos
authors.forename: Donald F
authors.initials: DF
authors.lastname: Sellitti
authors.forename: Tania C
authors.initials: TC
authors.lastname: Pithon-Curi
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000178:diet therapy / Q000378:metabolism; D019587:Dietary Supplements; D005973:Glutamine / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D011506:Proteins; D059748:Proteolysis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D011506:Proteins; D005973:Glutamine