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 receptor