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

Abstract

The objective of the study was to investigate the role of cholecystokinin (CCK) on the food-induced insulin sensitization phenomenon in healthy Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats. Whole body insulin sensitivity determined by hyperinsulinaemic euglycaemic glucose clamping and the rapid insulin sensitivity test served as endpoints. Determinations were done in both fasted and re-fed animals. The involvement of CCK in post-prandial insulin sensitization was 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-prandial increase in insulin sensitivity was marked in LETO, but not in OLETF rats. Intravenous proglumide attenuated post-prandial insulin sensitivity in LETO rats, with no effect in OLETF rats. Nevertheless, baseline insulin sensitivity was much lower in OLETF than in LETO rats. Treatment with rosiglitazone increased baseline insulin sensitivity of 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-prandial insulin sensitivity. The data obtained with OLETF rats strongly suggest the predominant role of CCK-1 receptors.