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/m(2); and waist circumference, 85 +/- 2 vs. 99 +/- 6 cm, respectively] were given iv infusions with atropine (15 mu g/kg bolus, 4 mu g/kg . h infusion), physostigmine (0.12 mu g/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/m(2) . 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. (J Clin Endocrinol Metab 96: E1843-E1847, 2011)