PMID- 30497927 OWN - NLM STAT- MEDLINE DCOM- 20190314 LR - 20190314 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 29 IP - 1 DP - 2019 Jan TI - Caloric restriction attenuates aging-induced cardiac insulin resistance in male Wistar rats through activation of PI3K/Akt pathway. PG - 97-105 LID - S0939-4753(18)30275-8 [pii] LID - 10.1016/j.numecd.2018.09.005 [doi] AB - BACKGROUND AND AIM: Caloric restriction (CR) improves insulin sensitivity and is one of the dietetic strategies most commonly used to enlarge life and to prevent aging-induced cardiovascular alterations. The aim of this study was to analyze the possible beneficial effects of caloric restriction (CR) preventing the aging-induced insulin resistance in the heart of male Wistar rats. METHODS AND RESULTS: Three experimental groups were used: 3 months old rats (3m), 24 months old rats (24m) and 24 months old rats subjected to 20% CR during their three last months of life (24m-CR). After sacrifice hearts were mounted in a perfusion system (Langendorff) and heart function in basal conditions and in response to accumulative doses of insulin (10(-9)-10(-7) M), in the presence or absence of Wortmannin (10(-6) M), was recorded. CR did not attenuate the aging-induced decrease in coronary artery vasodilation in response to insulin administration, but it prevented the aging-induced downregulation of cardiac contractility (dp/dt) through activation of the PI3K/Akt intracellular pathway. Insulin stimulated in a greater extent the PI3K/Akt pathway vs the activation of the MAPK pathway and increased the protein expression of IR, GLUT-4 and eNOS in the hearts of 3m and 24m-CR rats, but not in the hearts of 24m rats. Furthermore, CR prevented the aging induced increase in endothelin-1 protein expression in myocardial tissue. CONCLUSION: In conclusion CR partially improves cardiac insulin sensitivity and prevents the aging induced decrease in myocardial contractility in response to insulin administration through activation of PI3K/Akt pathway. CI - Copyright (c) 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. FAU - Granado, M AU - Granado M AD - Departamento de Fisiologia, Facultad de Medicina, Universidad Autonoma de Madrid, Madrid, Spain; CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: miriam.granado@uam.es. FAU - Amor, S AU - Amor S AD - Departamento de Fisiologia, Facultad de Medicina, Universidad Autonoma de Madrid, Madrid, Spain. FAU - Martin-Carro, B AU - Martin-Carro B AD - Departamento de Fisiologia, Facultad de Medicina, Universidad Autonoma de Madrid, Madrid, Spain. FAU - Guerra-Menendez, L AU - Guerra-Menendez L AD - Departamento de Ciencias Medicas Basicas, Universidad San Pablo CEU, Madrid, Spain. FAU - Tejera-Munoz, A AU - Tejera-Munoz A AD - Departamento de Fisiologia, Facultad de Medicina, Universidad Autonoma de Madrid, Madrid, Spain. FAU - Gonzalez-Hedstrom, D AU - Gonzalez-Hedstrom D AD - Departamento de Fisiologia, Facultad de Medicina, Universidad Autonoma de Madrid, Madrid, Spain. FAU - Rubio, C AU - Rubio C AD - Departamento de Bioquimica y Biologia Molecular, Facultad de Ciencias, Universidad Autonoma de Madrid, Spain. FAU - Carrascosa, J M AU - Carrascosa JM AD - Departamento de Bioquimica y Biologia Molecular, Facultad de Ciencias, Universidad Autonoma de Madrid, Spain. FAU - Garcia-Villalon, A L AU - Garcia-Villalon AL AD - Departamento de Fisiologia, Facultad de Medicina, Universidad Autonoma de Madrid, Madrid, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180926 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Endothelin-1) RN - 0 (Glucose Transporter Type 4) RN - 0 (Insulin) RN - 0 (Slc2a4 protein, rat) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - EC 1.14.13.39 (Nos3 protein, rat) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Age Factors MH - Aging MH - Animal Nutritional Physiological Phenomena MH - Animals MH - *Caloric Restriction MH - Coronary Vessels/drug effects/enzymology/physiopathology MH - Disease Models, Animal MH - Endothelin-1/metabolism MH - Glucose Transporter Type 4/metabolism MH - Heart/*drug effects/physiopathology MH - Insulin/*pharmacology MH - *Insulin Resistance MH - Isolated Heart Preparation MH - Male MH - Myocardial Contraction/drug effects MH - Myocardium/*enzymology MH - Nitric Oxide Synthase Type III/metabolism MH - Phosphatidylinositol 3-Kinase/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Rats, Wistar MH - Signal Transduction/drug effects MH - Vasodilation/drug effects OTO - NOTNLM OT - Aging OT - Akt OT - Caloric restriction OT - Cardiovascular OT - Heart OT - Insulin OT - Langendorff OT - Rat EDAT- 2018/12/01 06:00 MHDA- 2019/03/15 06:00 CRDT- 2018/12/01 06:00 PHST- 2018/04/24 00:00 [received] PHST- 2018/09/14 00:00 [revised] PHST- 2018/09/18 00:00 [accepted] PHST- 2018/12/01 06:00 [pubmed] PHST- 2019/03/15 06:00 [medline] PHST- 2018/12/01 06:00 [entrez] AID - S0939-4753(18)30275-8 [pii] AID - 10.1016/j.numecd.2018.09.005 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2019 Jan;29(1):97-105. doi: 10.1016/j.numecd.2018.09.005. Epub 2018 Sep 26.