Increased proportion of plasma apoB-48 to apoB-100 in non-insulin-dependent diabetic rats: contribution of enhanced apoB mRNA 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 and intestine from GK (Goto-Kakizaki) rats, a genetically NIDDM animal. Male GK rats and control littermates, aged 25 weeks, were used in this study. Ventromedial hypothalamus (VMH)-lesioned control rats were used as hyperinsulinemic models. VMH-lesioned GK rats (GK+VMH) were treated as an insulin-exhausted NIDDM model. Plasma cholesterol and triglyceride levels were increased in GK rats. Very low density lipoprotein (VLDL)-triglyceride and low density lipoprotein (LDL)-cholesterol concentrations were significantly higher in GK rats than in controls. The increase of VLDL-triglyceride was most marked in GK+VMH rats. Plasma apoB-48 levels, quantified by immunoblot, were increased in GK rats. However, apoB-100 levels were minimally elevated in GK rats. Therefore, the apoB-48/apoB-100 ratio was remarkably increased in GK rats. ApoB mRNA editing was analyzed by reverse transcriptase-polymerase chain reaction coupled with dideoxynucleotide chain termination assay. The ratio of apoB-48-type cDNA to apoB-100-type cDNA was significantly increased 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 GK and control littermates. ApoB mRNA in the intestine was almost totally edited (approximately 95%). Intestinal apoB-48/apoB-100 cDNA ratio showed no significant difference among the four groups. In conclusion, an enhanced apoB mRNA editing was indicated in the non-insulin-dependent diabetic rats, which might contribute to the increase of plasma apoB-48 levels.
Yamane
M
M
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Jiao
S
S
Kihara
S
S
Shimomura
I
I
Yanagi
K
K
Tokunaga
K
K
Kawata
S
S
Odaka
H
H
Ikeda
H
H
Yamashita
S
S
D000818:Animals; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D007031:Hypothalamus / Q000601:surgery; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009765:Obesity; D010179:Pancreas / Q000378:metabolism; D017393:RNA Editing; D051381:Rats; D011922:Rats, Mutant Strains
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D001786:Blood Glucose; D007328:Insulin