PMID- 18514627 OWN - NLM STAT- MEDLINE DCOM- 20080724 LR - 20211203 IS - 0002-9149 (Print) IS - 0002-9149 (Linking) VI - 101 IP - 11A DP - 2008 Jun 2 TI - Amino acid supplementation counteracts metabolic and functional damage in the diabetic rat heart. PG - 49E-56E LID - 10.1016/j.amjcard.2008.03.001 [doi] AB - We aimed to assess whether a specific mixture of amino acid (AA) supplements counteracts the metabolic and functional changes in the streptozotocin (STZ)-induced diabetic rat heart model. Adult male Wistar rats were divided into 6 groups (n = 10 each) and treated for 43 days: nondiabetic controls, nondiabetic rats given an AA mixture (0.1 g/kg per day), diabetic rats (induced with 65 mg/kg STZ given intraperitoneally), diabetic rats given AAs, diabetic rats given insulin (5 IU/day given subcutaneously), and diabetic rats given insulin plus AAs. During treatment, glycemia and insulinemia levels were measured in all groups. Changes in enzyme (reduced nicotinamide adenine dinucleotide-dehydrogenase, cytochrome c oxidase) activities and myosin heavy chain (MHC) composition were measured in the left ventricle. In 5 rats contractile function was assessed by measuring maximal shortening velocity of skinned ventricular trabeculae and the expression of translational regulator mammalian target of rapamycin (mTOR) was also found. STZ-induced diabetes was associated with reduced myocardial contractility, overall loss of oxidative capacity, a shift toward a slower MHC phenotype, and decreased mTOR tissue content. All of these changes appeared to be reversible with insulin. AA supplements partially restored the myocardial and oxidative dysfunction and also increased mTOR tissue content. The combination of insulin and AAs did not have a synergistic effect on either enzymatic or functional profiles. We conclude that AA supplements may contribute to restoring the oxidative and contractile dysfunction of diabetic rat hearts, probably through an mTOR-insulin independent mechanism. FAU - Pellegrino, Maria Antonietta AU - Pellegrino MA AD - Department of Experimental Medicine, Human Physiology Unit, University of Pavia, Pavia, Italy. FAU - Patrini, Cesare AU - Patrini C FAU - Pasini, Evasio AU - Pasini E FAU - Brocca, Lorenza AU - Brocca L FAU - Flati, Vincenzo AU - Flati V FAU - Corsetti, Giovanni AU - Corsetti G FAU - D'Antona, Giuseppe AU - D'Antona G LA - eng PT - Journal Article PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 0 (Amino Acids) RN - 0 (Carrier Proteins) RN - 0 (Eif4ebp1 protein, rat) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Phosphoproteins) RN - EC 1.9.3.1 (Electron Transport Complex IV) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases) RN - EC 2.7.11.1 (Rps6kb1 protein, rat) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Amino Acids/*administration & dosage MH - Animals MH - Blotting, Western MH - Carrier Proteins/metabolism MH - Diabetes Mellitus, Experimental/metabolism/*physiopathology MH - *Dietary Supplements MH - Electron Transport Complex IV/metabolism MH - Heart/*drug effects MH - Intracellular Signaling Peptides and Proteins MH - Male MH - Myocardium/*metabolism MH - Phosphoproteins/metabolism MH - Phosphorylation MH - Protein Kinases/metabolism MH - Rats MH - Rats, Wistar MH - Ribosomal Protein S6 Kinases/metabolism MH - Signal Transduction/physiology MH - TOR Serine-Threonine Kinases MH - Ventricular Function/*drug effects EDAT- 2008/07/02 09:00 MHDA- 2008/07/25 09:00 CRDT- 2008/07/02 09:00 PHST- 2008/07/02 09:00 [pubmed] PHST- 2008/07/25 09:00 [medline] PHST- 2008/07/02 09:00 [entrez] AID - S0002-9149(08)00396-2 [pii] AID - 10.1016/j.amjcard.2008.03.001 [doi] PST - ppublish SO - Am J Cardiol. 2008 Jun 2;101(11A):49E-56E. doi: 10.1016/j.amjcard.2008.03.001.