Amino acid supplementation counteracts metabolic and functional damage in the diabetic rat heart.
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.
Pellegrino
Maria Antonietta
MA
Department of Experimental Medicine, Human Physiology Unit, University of Pavia, Pavia, Italy.
Patrini
Cesare
C
Pasini
Evasio
E
Brocca
Lorenza
L
Flati
Vincenzo
V
Corsetti
Giovanni
G
D'Antona
Giuseppe
G
D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D019587:Dietary Supplements; D003576:Electron Transport Complex IV / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D016276:Ventricular Function / Q000187:drug effects*
D000596:Amino Acids; D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D003576:Electron Transport Complex IV; D011494:Protein Kinases; C546842:MTOR protein, human; C546845:mTOR protein, rat; D019893:Ribosomal Protein S6 Kinases; C526901:Rps6kb1 protein, rat; D058570:TOR Serine-Threonine Kinases