PMID- 29055722
OWN - NLM
STAT- MEDLINE
DCOM- 20190517
LR  - 20190517
IS  - 1873-6815 (Electronic)
IS  - 0531-5565 (Linking)
VI  - 109
DP  - 2018 Aug
TI  - Study of insulin vascular sensitivity in aortic rings and endothelial cells from 
      aged rats subjected to caloric restriction: Role of perivascular adipose tissue.
PG  - 126-136
LID - S0531-5565(17)30591-0 [pii]
LID - 10.1016/j.exger.2017.10.017 [doi]
AB  - The prevalence of metabolic syndrome is dramatically increasing among elderly 
      population. Metabolic syndrome in aged individuals is associated with 
      hyperinsulinemia and insulin resistance both in metabolic tissues and in the 
      cardiovascular system, with this fact being associated with the cardiometabolic 
      alterations associated to this condition. 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 CR in aging-induced 
      vascular insulin resistance both in aortic rings and in primary culture of 
      endothelial cells. In addition, the inflammatory profile of perivascular adipose 
      tissue (PVAT) and its possible role in the impairment of vascular insulin 
      sensitivity associated with aging was also assessed. Three experimental groups of 
      male Wistar rats were used: 3 (3m), 24 (24m) fed ad libitum and 24months old rats 
      subjected to 20% CR during their three last months of life (24m-CR). Aorta rings 
      surrounded or not by PVAT were mounted in an organ bath and precontracted with 
      phenylephrine (10(-7.5)M). Changes in isometric tension were recorded in response 
      to cumulative insulin concentrations (10(-8)-10(-5.5)M) in the presence or 
      absence of L-NAME (10(-4)M). Aortic rings and primary aortic endothelial cells 
      were incubated in presence/absence of insulin (10(-7)M) and the activation of the 
      PI3K/Akt and MAPK pathways as well as nitrite and nitrates concentrations and the 
      mRNA levels of eNOS, insulin receptor, and GLUT-4 were assessed. CR prevented the 
      aging-induced decrease in the vasodilator response to insulin and the 
      aging-induced increase in the vasoconstrictor response to high insulin 
      concentrations. Changes between 24m and 24m-CR aorta rings were abolished in the 
      presence of L-NAME. CR induced-improvement in insulin vascular sensitivity was 
      related with activation of the PI3K/Akt both in aortic rings and in aortic 
      endothelial cells in response to insulin. CR attenuated the overexpression of 
      iNOS, TNF-alpha and IL-1beta in the PVAT of aged rats although aortic rings surrounded 
      by PVAT from 24m rats showed and increased vasorelaxation in response to insulin 
      compared to aortic rings from 3m and 24m-CR rats. In conclusion, a moderate 
      protocol of CR improves insulin vascular sensitivity and prevents the aging 
      induced overexpression of pro-inflammatory cytokines in PVAT.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Amor, S
AU  - Amor S
AD  - Departamento de Fisiologia, Facultad de Medicina, Universidad Autonoma de Madrid, 
      Spain.
FAU - Martin-Carro, B
AU  - Martin-Carro B
AD  - Departamento de Fisiologia, Facultad de Medicina, Universidad Autonoma de 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 - Hu, W
AU  - Hu W
AD  - School of Biomedical Sciences, Institute of Vascular Medicine, Faculty of 
      Medicine, Chinese University of Hong Kong, China.
FAU - Huang, Y
AU  - Huang Y
AD  - School of Biomedical Sciences, Institute of Vascular Medicine, Faculty of 
      Medicine, Chinese University of Hong Kong, China.
FAU - Garcia-Villalon, A L
AU  - Garcia-Villalon AL
AD  - Departamento de Fisiologia, Facultad de Medicina, Universidad Autonoma de Madrid, 
      Spain.
FAU - Granado, M
AU  - Granado M
AD  - Departamento de Fisiologia, Facultad de Medicina, Universidad Autonoma de Madrid, 
      Spain; CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos 
      III, Madrid, Spain. Electronic address: miriam.granado@uam.es.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171018
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Adipose Tissue/*metabolism
MH  - Aging/*physiology
MH  - Animals
MH  - Aorta/*drug effects/physiology
MH  - *Caloric Restriction
MH  - Cells, Cultured
MH  - Endothelial Cells/*drug effects/physiology
MH  - *Insulin Resistance
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Vasoconstriction/drug effects
OTO - NOTNLM
OT  - Aging
OT  - Akt
OT  - Aorta
OT  - Insulin
OT  - Perivascular adipose tissue
OT  - eNOS
EDAT- 2017/10/23 06:00
MHDA- 2019/05/18 06:00
CRDT- 2017/10/23 06:00
PHST- 2017/08/04 00:00 [received]
PHST- 2017/10/15 00:00 [revised]
PHST- 2017/10/16 00:00 [accepted]
PHST- 2017/10/23 06:00 [pubmed]
PHST- 2019/05/18 06:00 [medline]
PHST- 2017/10/23 06:00 [entrez]
AID - S0531-5565(17)30591-0 [pii]
AID - 10.1016/j.exger.2017.10.017 [doi]
PST - ppublish
SO  - Exp Gerontol. 2018 Aug;109:126-136. doi: 10.1016/j.exger.2017.10.017. Epub 2017 
      Oct 18.