ACCELERATED LOSS OF ISLET BETA-CELLS IN SUCROSE-FED GOTO-KAKIZAKI RATS, A GENETIC MODEL OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS

The Goto-Kakizaki (GK) rat is a spontaneously diabetic animal model of non-insulin-dependent diabetes mellitus, which is characterized by pr ogressive loss of beta cells in the pancreatic islets with fibrosis. I n the present study, we examined the effects of sucrose feeding on the islet pathology in this model, Six-week-old GIC rats were fed with 30 % sucrose for 6 weeks to induce severe hyperglycemia, and their condit ion was compared with that of nontreated rats. Age-matched normal Wist ar rats were also given sucrose for the same periods and used for comp arison. The sucrose-treated GK rats showed elevated blood glucose leve ls on oral glucose tolerance tests at 60 minutes and 120 minutes, repr esenting 123% and 127% of values in untreated GK rats, respectively. A t the end of the study, the mean beta-cell volume density in GK rats w as 50% less than that in untreated Wistar rats. Sucrose feeding furthe r reduced the volume densities of beta cells to only 50% of the levels of age-matched GB rats. Apoptotic cells were found in islet beta cell s only in GK rats fed sucrose (mean 0.067%). There appeared to be more islets that immunohistochemically stained strongly positive with 8-hy droxy-deoxyguanosine as a marker of oxidative damage of DNA in GK rats fed sucrose compared with those not gives sucrose, GK rats not fed su crose showed significantly lower proliferative activity of beta cells measured by 5-bromo-2'-deoxyuridine uptake and intensified expression of Bcl-2 immunoreactivities at 6 weeks of age compared with those in a ge-matched Wistar rats. These two indices were reduced in both GK and Wistar rats with increasing age and were not affected by sucrose feedi ng in either group. The present study thus indicated that sucrose feed ing promoted the apoptosis of beta cells in GK rats through increased oxidative stress without altering their proliferative activity.