Impaired Hepatic Apolipoprotein B and E Translation in Streptozotocin Diabetic Rats

Studies of streptozotocin-induced diabetes in rats have demon-strated that hepatic apo B and apo E production are reduced. To determine if reductions are related to decreases in hepatic mRNAs, we performed blotting analysis of total liver RNA with rat apo B, apo E, and albumin cDNA probes. The expected reduction in albumin mRNA levels to 48 % of control livers occurred in diabetic rat liver, while apo B and apo E mRNA levels were unchanged. The proportion of translational stop codon (BSTOP) mRNA averaged 43 % of total in diabetic rats similar to control levels. Long-term labeling experiments using JISlmethionine in primary cultures of rat hepatocytes and spe-cific immunoprecipitations demonstrated production of apo B and apo E, and albumin by hepatocytes from diabetic rats was reduced to 37%, 53%, and 23 % of controls. Pulse-chase studies, together with mRNA analyses, suggest that reduced hepatic secretion ofapo B and apo E in diabetics is primarily a result of impaired translation and not intracellular degradation. Ribo-some transit studies directly confirmed the prolonged elonga-tion rates for apo B and apo E mRNAs in hepatocytes derived from diabetic rats. This effect was more pronounced on apo BH (higher molecular weight) than on apo BL (lower molecular weight). Treatment of diabetic rats with insulin for 7 d led to normalization of hepatic albumin mRNA levels with no sub-stantial change in apo E mRNA levels. In contrast, insulin treatment resulted in significant increases in hepatic apo B mRNA over control levels. Results suggest hepatic albumin and apo B mRNA levels are responsive to insulin in the diabeti