Activation of the GLP-1 Receptor by Liraglutide Increases ACE2 Expression, Reversing Right Ventricle Hypertrophy, and Improving the Production of SP-A and SP-B in the Lungs of Type 1 Diabetes Rats.
Endocrinology
; 156(10): 3559-69, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26196539
ABSTRACT
Diabetes alters microvascular function in the vascular beds of organs, including the lungs. Cardiovascular complications of pulmonary vascular affectation may be a consequence of the overactivation of the vasoconstrictive and proliferative components of the renin-angiotensin system. We previously reported that pulmonary physiology and surfactant production is improved by the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide (LIR) in a rat model of lung hypoplasia. Because we hypothesized that streptozotocin-induced diabetes rats would show deficiencies in lung function, including surfactant proteins, and develop an imbalance of the renin-angiotensin system in the lungs. This effect would in turn be prevented by long-acting agonists of the GLP-1R, such as LIR. The induction of diabetes reduced the surfactant protein A and B in the lungs and caused the vasoconstrictor component of the renin-angiotensin system to predominate, which in turn increased angiotensin II levels, and ultimately being associated with right ventricle hypertrophy. LIR restored surfactant protein levels and reversed the imbalance in the renin-angiotensin system in this type 1 diabetes mellitus rat model. Moreover, LIR provoked a strong increase in angiotensin-converting enzyme 2 expression in the lungs of both diabetic and control rats, and in the circulating angiotensin(1-7) in diabetic animals. These effects prompted complete reversion of right ventricle hypertrophy. The consequences of LIR administration were independent of glycemic control and of glucocorticoids, and they involved NK2 homeobox 1 signaling. This study demonstrates by first time that GLP-1R agonists, such as LIR, might improve the cardiopulmonary complications associated with diabetes.
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Base de dados:
MEDLINE
Assunto principal:
Peptidil Dipeptidase A
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Proteína A Associada a Surfactante Pulmonar
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Proteína B Associada a Surfactante Pulmonar
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Diabetes Mellitus Tipo 1
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Liraglutida
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Receptor do Peptídeo Semelhante ao Glucagon 1
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article