Rationale: Cholecystokinin type B (CCK(B)) receptor agonists such as pentagastrin or CCK-4 have panic-like anxiogenic effects in humans. It has also been shown that CCK-4 can stimulate insulin release and thus C-peptide release from pancreatic islet cells. Combined, these mechanisms may provide a basis for a bioassay.
Objectives: Our aim was to study if a pentagastrin bolus injection evokes insulin release (as measured by C-peptide) and if the levels of C-peptide correlate to the anxiogenic effect of pentagastrin.
Methods: Pentagastrin was given in bolus IV injections to healthy volunteers at increasing doses (0.003, 0.012, 0.05 and 0.2 microg/kg).
Results: A significant increase in the plasma level of C-peptide was observed 2-4 min after the highest dose of pentagastrin. This increase was accompanied by a transient panic-like anxiety within 2 min following pentagastrin, measured using a state anxiety scale. Also, 0.05 microg/kg pentagastrin gave a minor but significant subjective discomfort at the same time interval. The basal plasma level of C-peptide preceding the pentagastrin injection showed a positive correlation to the intensity of the subsequent pentagastrin-induced panic-like anxiety as rated on the state anxiety scale. In addition, basal plasma levels of cortisol were positively correlated to the subsequent pentagastrin-induced increase in plasma C-peptide levels.
Conclusions: Our results imply a possible relationship between insulin/C-peptide release and sensitivity to psychotropic activation by CCK(B) receptor stimulation. Furthermore, we postulate that both basal and pentagastrin-induced plasma levels of C-peptide may possess characteristic phenotype properties for anxiety related traits.