Involvement of cholecystokinin in baseline and post-prandial whole body insulin sensitivity in rats

The objective of the study was to investigate the role of cholecystokinin(CCK) on the food-induced insulin sensitizationphenomenon in healthy Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats. Whole body insulin sensitivitydetermined by hyperinsulinaemic euglycaemic glucose clamping and the rapid insulin sensitivitytest served as endpoints. Determinations were done in both fasted and re-fed animals. The involvement of CCK in post-prandialinsulin sensitizationwas assessed by using proglumide, a CCK receptor blocker, by assessment of hypothalamic CCK-1/CCK-2 receptor expression by rt-PCR technique and by plasma insulin immunoreactivity determinations by means of radioimmunoassay as pharmacological, genetic and analytical approaches, respectively. The body weight of the OLETF rats and the amount of food consumed much exceeded those seen with LETO rats. The post-prandialincrease in insulin sensitivitywas marked in LETO, but not in OLETF rats. Intravenous proglumideattenuated post-prandialinsulin sensitivityin LETO rats, with no effect in OLETF rats. Nevertheless, baseline insulin sensitivitywas much lower in OLETF than in LETO rats. Treatment with rosiglitazoneincreased baseline insulin sensitivityof OLETF rats and evoked an increase in CCK-1 receptor gene expression in LETO rats. The results provide evidence for the involvement of CCK receptors in adjustment of both fasting and post-prandialinsulin sensitivity. The data obtained with OLETF rats strongly suggest the predominant role of CCK-1 receptors.