Figure 6.

Insulin decreased neuronal M2 muscarinic receptor function in obese-prone and obese-resistant rats on a high-fat diet. Neuronal M₂ muscarinic receptor function was measured as the ability of pilocarpine, a selective muscarinic agonist, to inhibit vagally induced bronchoconstriction. Pilocarpine inhibited vagally induced bronchoconstriction in a dose-related manner, but the effect was significantly less in obese-prone (A, closed circles) than in obese-resistant (A, closed triangles) rats on a high-fat diet, demonstrating decreased function of inhibitory neuronal M₂ muscarinic receptor in obese-prone rats on a high-fat diet. Reducing insulin with STZ in obese-prone rats (B, open circles with solid line) significantly enhanced the ability of pilocarpine to inhibit vagally induced bronchoconstriction. Acute administration of insulin to STZ-treated rats (B, dashed line) reversed the effect of STZ. In obese-resistant rats, reducing insulin with STZ (C, open triangles with solid line) did not change the ability of pilocarpine to inhibit vagally induced bronchoconstriction. However, in these rats, supplemental insulin significantly reduced the ability of pilocarpine to inhibit vagally induced bronchoconstriction (C, dashed line), similar to obese-prone rats on a high-fat diet (A, closed circle). Each point represents the mean, and vertical bars show SEM. *P < 0.05.