Estrogen Protects Cardiac Function and Energy Metabolism in Dilated Cardiomyopathy Induced by Loss of Cardiac IRS1 and IRS2.
diabetic cardiomyopathy
energy metabolism
estradiol
estrogen
insulin resistance
Journal
Circulation. Heart failure
ISSN: 1941-3297
Titre abrégé: Circ Heart Fail
Pays: United States
ID NLM: 101479941
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
pubmed:
18
5
2022
medline:
24
6
2022
entrez:
17
5
2022
Statut:
ppublish
Résumé
Type 2 diabetes (T2D) is a high-risk factor for incident of cardiovascular diseases. Women at young ages show a reduced incidence of both T2D and cardiovascular diseases compared with men, but these disparities disappear in postmenopausal women versus age-matched men. Thus, ovaries and ovarian hormones, such as estrogen, are expected to protect from T2D and cardiovascular diseases. In this study, we aimed to investigate the role of ovaries and ovarian hormone estrogen in cardiac function and energy metabolism using the cardiac IRS (insulin receptor substrate) 1 and IRS2 double genes knockout mice that mimic cardiac insulin resistance. Control and heart-specific IRS1/2 double genes knockout mice were treated with placebo or 17β-estradiol (E All male heart-specific IRS1/2 double genes knockout mice died of heart failure at 6 to 8 weeks as we previously described (Qi et al), but all female heart-specific IRS1/2 double genes knockout mice survived >1 year. Removal of ovaries in heart-specific IRS1/2 double genes knockout female mice resulted in cardiac dysfunction, and ultimately animal death. However, E These results show that estrogen protects mice from cardiac insulin resistance-induced diabetic cardiomyopathy. This may provide a fundamental mechanism for the gender difference for the incidence of both T2D and cardiovascular diseases. This study highlights that estrogen signaling could be a potential target for improving cardiac function and energy metabolism in humans with T2D.
Sections du résumé
BACKGROUND
Type 2 diabetes (T2D) is a high-risk factor for incident of cardiovascular diseases. Women at young ages show a reduced incidence of both T2D and cardiovascular diseases compared with men, but these disparities disappear in postmenopausal women versus age-matched men. Thus, ovaries and ovarian hormones, such as estrogen, are expected to protect from T2D and cardiovascular diseases. In this study, we aimed to investigate the role of ovaries and ovarian hormone estrogen in cardiac function and energy metabolism using the cardiac IRS (insulin receptor substrate) 1 and IRS2 double genes knockout mice that mimic cardiac insulin resistance.
METHODS
Control and heart-specific IRS1/2 double genes knockout mice were treated with placebo or 17β-estradiol (E
RESULTS
All male heart-specific IRS1/2 double genes knockout mice died of heart failure at 6 to 8 weeks as we previously described (Qi et al), but all female heart-specific IRS1/2 double genes knockout mice survived >1 year. Removal of ovaries in heart-specific IRS1/2 double genes knockout female mice resulted in cardiac dysfunction, and ultimately animal death. However, E
CONCLUSIONS
These results show that estrogen protects mice from cardiac insulin resistance-induced diabetic cardiomyopathy. This may provide a fundamental mechanism for the gender difference for the incidence of both T2D and cardiovascular diseases. This study highlights that estrogen signaling could be a potential target for improving cardiac function and energy metabolism in humans with T2D.
Identifiants
pubmed: 35579013
doi: 10.1161/CIRCHEARTFAILURE.121.008758
pmc: PMC9675316
mid: NIHMS1796441
doi:
Substances chimiques
Estrogens
0
IRS1 protein, human
0
IRS2 protein, human
0
Insulin Receptor Substrate Proteins
0
Irs2 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e008758Subventions
Organisme : NIA NIH HHS
ID : K01 AG056848
Pays : United States
Organisme : NHLBI NIH HHS
ID : R00 HL132123
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK095118
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124588
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL153164
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG064869
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120968
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK118334
Pays : United States
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