Increased proportion of plasma apoB-48 to apoB-100 in non-insulin-dependent diabetic rats: contribution of enhanced apoB mRNA editing in the liver.

M Yamane,S Jiao,S Kihara,I Shimomura,K Yanagi,K Tokunaga,S Kawata,H Odaka,H Ikeda,S Yamashita

doi:10.1016/s0022-2275(20)41487-7

Abstract

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.

Highlights

To assess the alteration of apolipoprotein B mRNA editing in non-insulindependent diabetes mellitus (NIDDM),we measured plasma apoB-100 and apoB48 levels and apoB ml7NA editing efficiency in the liver and intestine from GK (Goto-Kakizaki)rats, a genetically NIDDM animal
Fasting plasma glucose and insulin concentrations were significantlyhigher in GK rats than those in control littermates as shown in Table 1(P< 0.001 and P < 0.01, respectively).In GK + Ventromedial hypothalamus (VMH) rats, plasma glucose levels were further increased to 19.2 mmol/L in average, the mean IR1 levels were decreased from 81 pU/ml in GK to 53pU/ml (P< 0.05).Plasma cholesterol and triglyceride concentrations were increased in GK rats (P< 0.01 and P < 0.05, respectively)and again were further elevated in GK + VMH
Food intakes of VMH, GK, and GK + VMH rats were increased by 20%, 30%, and 30%,respectively,compared with controls

Summary

Introduction

To assess the alteration of apolipoprotein (apo) B mRNA editing in non-insulindependent diabetes mellitus (NIDDM),we measured plasma apoB-100 and apoB48 levels and apoB ml7NA editing efficiency in the liver and intestine from GK (Goto-Kakizaki)rats, a genetically NIDDM animal. The development of the VMH lesion increased plasma apoB48 levels, it had no effect on the proportion of apoB48-type to apoB-100-typecDNA in the liver from both GK and control littermates. M 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., S. Increased proportion of plasma apoB48 to apoB-100 in non-insulindependent diabetic rats: contribution of enhanced apoB mRNA editing in the liver.J. Lipid Res. 1995.36: 1676- 1685. ‘To whom correspondence should be addressed at: Second Department of Internal Medicine, Osaka University Medical School, 2-2, Yamadaoka, Suita, Osaka 565,Japan This enzyme is thought to be an essentialfactor.contro1ling the absorption of dietary cholesterol [4], we speculate that cholesterolabsorption is enhanced in diabetes, resulting in a marked accumulation of chylomicron remnants in the circulation, especially under the condition of cholesterol feeding

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