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- W3096402561 abstract "Rationale: Obesity-related asthma responds poorly to current treatments, leading to an urgent need for better medications. Obesity is associated with insulin resistance and increased insulin. Vagus nerve-mediated airway hyperreactivity in obese rats is potentiated by increased insulin and inhibited by reducing insulin levels. Here we tested whether lowering insulin with a hypoglycemic drug, pioglitazone, reduces airway hyperreactivity in diet-induced obese rats. Methods: Male rats were fed a high (60%) or low (10%) fat diet for 5 weeks ± pioglitazone (3 mg/kg, gavage daily). Airway hyperreactivity was tested by measuring bronchoconstriction in response to vagus nerve stimulation in anesthetized, paralyzed, vagotomized and ventilated rats. Inhibitory M2 muscarinic receptors normally limit ACh release from parasympathetic nerves, and their function was tested by measuring whether pilocarpine, a muscarinic agonist, inhibits vagus nerve-induced bronchoconstriction. M3 muscarinic receptor function on airway smooth muscle was tested by measuring bronchoconstriction induced by methacholine. Body fat, fasting glucose and insulin were measured by nuclear magnetic resonance, glucose meter and ELISA respectively. Results: Airway hyperreactivity was significantly potentiated in diet induced obese rats, and was inhibited by pioglitazone. M2 receptor function was reduced in obese rats but also restored by pioglitazone. M3 receptor function was not different across animal groups. Pioglitazone significantly reduced fasting insulin, but not body weight, body fat, or fasting glucose in obese rats. Conclusions: Pioglitazone can inhibit airway hyperreactivity in obese rats via reducing insulin and protecting M2 receptor function." @default.
- W3096402561 created "2020-11-09" @default.
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- W3096402561 date "2020-09-07" @default.
- W3096402561 modified "2023-09-25" @default.
- W3096402561 title "Pioglitazone inhibits obesity-related airway hyperreactivity" @default.
- W3096402561 doi "https://doi.org/10.1183/13993003.congress-2020.2904" @default.
- W3096402561 hasPublicationYear "2020" @default.
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