Metformin prevents airway hyperreactivity in rats with dietary obesity
Increased 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 potentiation of vagally-induced airway hyperreactivity. These data suggest that medications that target insulin may be effective treatment for obesity-related asthma.