INCREASED PROPORTION OF PLASMA APO-B-48 TO APO-B-100 IN NON-INSULIN-DEPENDENT DIABETIC RATS - CONTRIBUTION OF ENHANCED APO-B MESSENGER-RNA EDITING IN THE LIVER

To assess the alteration of apolipoprotein (apo) B mRNA editing in non -insulin-dependent diabetes mellitus (NIDDM), we measured plasma apoB- 100 and apoB-48 levels and apoB mRNA editing efficiency in the liver a nd intestine from GK (Goto-Kakizaki) rats, a genetically NIDDM animal. Male GK rats and control littermates, aged 25 weeks, were used in thi s study. Ventromedial hypothalamus (VMH)-lesioned control rats were us ed as hyperinsulinemic models. VMH-lesioned GK rats (GK + VMH) were tr eated as an insulin-exhausted NIDDM model. Plasma cholesterol and trig lyceride levels were increased in GK rats. Very low density lipoprotei n (VLDL)-triglyceride and low density lipoprotein (LDL)-choiesterol co ncentrations were significantly higher in GK rats than in controls. Th e increase of VLDL-triglyceride was most marked in GK + VMH rats. Plas ma apoB-48 levels, quantified by immunoblot, were increased in GK rats . However, apoB-100 levels were minimally elevated in GEL rats. Theref ore, the apoB-48/apoB-100 ratio was remarkably increased in GK rats. A poB mRNA editing was analyzed by reverse transcriptase-polymerase chai n reaction coupled with dideoxynucleotide chain termination assay. The ratio of apoB-48-type cDNA to apoB-100-type cDNA was significantly in creased in the liver from GK rats compared with controls. Although the development of the VMH lesion increased plasma apoB-48 levels, it had no effect on the proportion of apoB-48-type to apoB-100-type cDNA in the liver from both GR and control littermates. ApoB mRNA in the intes tine was almost totally edited (similar to 95%). Intestinal apoB-48/ap oB-100 cDNA ratio showed no significant difference among the four grou ps. In conclusion, an enhanced apoB mRNA editing was indicated in the non-insulin-dependent diabetic rats, which might contribute to the inc rease of plasma apoB-48 levels.