title: Atropine improves insulin sensitivity in both lean and abdominally obese subjects.
abstract: 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.
  
  
  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 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/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, SE-413 35 Gothenburg, Sweden. maria.svensson@wlab.gu.se
authors.forename: M K
authors.initials: MK
authors.lastname: Svensson
authors.forename: P-A
authors.initials: PA
authors.lastname: Jansson
authors.forename: A L
authors.initials: AL
authors.lastname: Persson
authors.forename: M
authors.initials: M
authors.lastname: Sjöstrand
authors.forename: J W
authors.initials: JW
authors.lastname: Eriksson
mesh_terms: D000328:Adult; D001285:Atropine / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000503:physiopathology*; D010276:Parasympatholytics / Q000494:pharmacology*; D016037:Single-Blind Method
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010276:Parasympatholytics; D001285:Atropine