Troglitazone stimulates pancreatic growth in congenitally CCK-A receptor-deficient OLETF rats

We examined the effect of troglitazone treatment on pancreatic growth in th e CCK-A receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rat, a n animal model for type 2 diabetes mellitus. A troglitazone-rich diet (0.2% ) was given from 12 to 28 wk of age or from 12 or 28 wk of age to 72 wk of age. Fasting serum glucose concentrations in control OLETF rats increased p rogressively with age, which was almost completely prevented by troglitazon e treatment. Insulin levels in serum and pancreatic content in the control rat markedly increased at 28 wk of age but significantly decreased at 72 wk of age compared with those at 12 wk of age, whereas those in troglitazone- treated rats were nearly the same at all ages and were similar to those in control rats at 12 wk of age. Pancreatic wet weight in control rats decreas ed with age irrespective of whether they were hyperinsulinemic (28 wk old) or hypoinsulinemic (72 wk old). Troglitazone treatment significantly increa sed pancreatic wet weight and protein, DNA, and enzyme contents compared wi th those in the control rats. Moreover, troglitazone treatment completely p revented or reversed histological alterations such as fibrosis, fatty repla cement, and inflammatory cell infiltration. Our results indicate that trogl itazone stimulates pancreatic growth in the congenitally CCK-A receptor-def icient OLETF rat not only by reducing insulin resistance and potentiating i nsulin action but also by suppressing inflammatory changes in the pancreas.