Exenatide Increases IL-1RA Concentration and Induces Nrf-2âKeap-1âRegulated Antioxidant Enzymes: Relevance to ß-Cell Function.
J Clin Endocrinol Metab
; 103(3): 1180-1187, 2018 03 01.
Article
em En
| MEDLINE
| ID: mdl-29346597
ABSTRACT
Purpose:
We previously demonstrated the anti-inflammatory and antioxidant effects of exenatide. We now hypothesized that exenatide also increases the plasma concentration of interleukin-1 receptor antagonist (IL-1RA), an endogenous anti-inflammatory protein, and modulates the nuclear factor erythroid 2ârelated factorâKelchlike ECH-associated protein 1âantioxidant response element (Nrf-2âKeap-1âARE) system to induce key antioxidant enzymes to suppress inflammatory and oxidative stress.Methods:
Twenty-four patients with obesity and type 2 diabetes receiving combined oral and insulin therapy were randomly assigned to receive either exenatide 10 µg or placebo twice a day for 12 weeks.Results:
Exenatide increased IL-1RA concentration by 61% (from 318 ± 53 to 456 ± 88 pg/mL; P < 0.05). Exenatide treatment also suppressed Keap-1 protein (P < 0.05) and increased messenger RNA expression of NQO-1, glutathione S-transferase PI, heme oxygenase-1, and p21 and increased NAD(P)H dehydrogenase [quinone] 1 protein (P < 0.05) in mononuclear cells.Conclusions:
Because IL-1RA protects, maintains, and stimulates ß-cell function in humans and Nrf-2âKeap-1âARE protects ß cells in animals with experimental diabetes, these actions of exenatide may contribute to a potential protective effect on ß cells in diabetes.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Peçonhas
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Diabetes Mellitus Tipo 2
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Proteína Antagonista do Receptor de Interleucina 1
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Hipoglicemiantes
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Obesidade
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article