Unconditioned and conditioned effects of intranasally administered insulin vs placebo in healthy men: a randomised controlled trial

Diabetologia - Clinical and Experimental Diabetes and Metabolism, 04/28/2011

The unconditioned blood glucose decrease on day 1 and the unconditioned and conditioned increases of peripheral insulin are indicative of brain–pancreas cross–talk. The conditionability of the hormonal responses reveals new applications for intranasal insulin.


  • In a randomised controlled trial, 32 healthy normal–weight men (mean age 24.2 [SEM 0.5], mean BMI 22.4 [0.3]) received a conditioned stimulus (CS) and six administrations of either soluble H–insulin 100 (20 U [0.2 ml]; group 1; n=16) or vehicle (0.2 ml; group 2; n=16) on day 1.
  • The CS was the tarry smell of meta–cresol (used as a stabilising vehicle in many insulin preparations and placebos).
  • On day 2, all participants received the CS and six administrations of placebo. Participants and experimenters were blinded to group assignment.
  • Sixteen individuals were randomised to and analysed in each group. Participants were sequentially numbered for group allocation.
  • The main outcome measures were blood glucose and insulin, expressed as cumulative difference–from–baseline changes.


  • While maintaining euglycaemia, intranasal insulin induced an increase of peripheral insulin on day 1 (group 1, 17.78 [21.88] pmol/l vs group 2, -10.24 [9.42] pmol/l), and also on day 2 when the CS was given with placebo (group 1, 12.53 [5.57] pmol/l vs group 2, -5.51 [6.16] pmol/l).
  • Moreover, a moderate reduction of blood glucose on day 1 (group 1, -0.54 [0.36] mmol/l vs group 2, 0.58 [0.48] mmol/l) was obtained (all p values <0.05).
  • There were no adverse side effects.

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