Metformin prevents airway hyperreactivity in rats with dietary obesity

Am J Physiol Lung Cell Mol Physiol. 2021 Oct 20. doi: 10.1152/ajplung.00202.2021. Online ahead of print.ABSTRACTIncreased insulin is associated with obesity-related airway hyperreactivity and asthma. We tested whether the use of metformin, an anti-diabetic drug used to reduce insulin resistance, can reduce circulating insulin, thereby preventing airway hyperreactivity in rats with dietary obesity. Male and female rats were fed a high- or low-fat diet for 5 weeks. Some male rats were simultaneously treated with metformin (100 mg/kg, p.o.). In separate experiments, after 5 weeks of a high-fat diet, some rats were switched to a low-fat diet, while others continued a high-fat diet for an additional 5 weeks. Bronchoconstriction and bradycardia in response to bilateral electrical vagus nerve stimulation or to inhaled methacholine were measured in anesthetized and vagotomized rats. Body weight, body fat, caloric intake, fasting glucose and insulin were measured. Vagally-induced bronchoconstriction was potentiated only in male rats on a high-fat diet. Males gained more body weight, body fat, and had increased levels of fasting insulin, compared to females. Metformin prevented development of vagally-induced airway hyperreactivity in male rats on high-fat diet, in addition to inhibiting weight gain, fat gain and increased insulin. In contrast, switching rats to a low-fat diet for 5 weeks reduced body weight and body fat, it did not reverse fasting glucose, fasting insulin or potentiati...

Source: Am J Physiol Lung Ce... - October 20, 2021 Category: Respiratory Medicine Authors: Gina N Calco Becky J Proskocil David B Jacoby Allison D Fryer Zhenying Nie Source Type: research