Comprehensive analysis of intranasal insulin pharmacokinetics and pharmacodynamics in the rat brain

Intranasal insulin and its therapeutic potential in Alzheimer’s disease have already been in the focus of clinical trials, but the exact role of insulin in the brain is still unknown. One of the main goals of this research is to clarify and explore the time-dependent regular insulin distribution and activity in the rat brain following intranasal administration. Insulin immediately distributes to all brain regions after intranasal administration and is instantly utilized and/or metabolized, with the most pronounced increment seen in temporal cortex. Intranasal insulin probably positively influences insulin secretion seen as increment of both C-peptide and insulin in the periphery and in distinctive brain regions (hypothalamus, temporal and parietal cortices and cerebellum). Results reveal secondary activation of AMP-activated protein kinase and calcium/calmodulin-dependent protein kinase, which could be due to the brain region-dependent negative feedback mechanism on the overstimulated insulin signalling pathway.