Atropine Improves Insulin Sensitivity in Both Lean and Abdominally Obese Subjects

Background: Dysregulated autonomic nerve activity may contribute to the development of type 2 diabetes. The aim of this study was to assess the effects of an anticholinergic agent, atropine, and a cholinergic agent, physostigmine, on insulin sensitivity in lean and abdominally obese subjects. Subjects and Methods: In a single-blinded three-way crossover study, six lean and six abdominally obese nondiabetic subjects [three males and three females in each group; age, 43.8 ± 14.8 vs. 46.8 ± 4.8 yr (mean ± sd); body mass index, 22.6 ± 1.7 vs. 28.8 ± 1.3 kg/m2; and waist circumference, 85 ± 2 vs. 99 ± 6 cm, respectively] were given iv infusions with atropine (15 μg/kg bolus, 4 μg/kg · h infusion), physostigmine (0.12 μg/kg · min) or saline (0.9% NaCl) in a randomized treatment order. Infusions were started 30 min before and continued throughout a 120-min euglycemic (5.6 mm) hyperinsulinemic (40 mU/m2 · min) clamp. Results: Insulin sensitivity (M-value, i.e. glucose infusion rate divided by lean body mass) during the last 60 min of the clamp was higher during infusion with atropine than saline (9.2 ± 1.0 vs. 7.6 ± 1.0 mg/kg lean body mass · min, mean ± sem; P = 0.015) in all subjects. Physostigmine did not differ significantly from saline (8.2 ± 1.0). M-values were significantly higher in lean vs. obese [atropine, 11.6 ± 1.4 vs. 7.6 ± 1.3; physostigmine, 10.8 ± 1.3 vs. 6.3 ± 1.3; and saline, 9.1 ± 1.4 vs. 6.4 ± 1.3, respectively (all P < 0.05)], but the incremental effect of atropine vs. saline did not differ consistently between groups. Conclusion: Insulin sensitivity was higher during a short-term atropine infusion compared with saline in both lean and abdominally obese subjects. This insulin-sensitizing effect of cholinergic blockade is unexpected, and the underlying mechanisms should be further investigated.