Isoforms of rat apolipoproteins and changes induced by insulin deficiency and fasting

Reasons for the disordered lipoprotein metabolism in insulin deficiency are not completely understood. In this study the apolipoproteins from plasma of fed and fasted streptozotocin-induced insulin-deficient rats were compared with normal control rats. Analysis of the apolipoprotein isoforms by two-dimensional electrophoresis revealed increased proportions of sialylated apo E and of sialylated apo C-III in diabetic rats compared with control rats. Fasting increased the proportion of sialylated apo E but not the proportion of sialylated apo C-III. 3H-labeled leucine was injected into normal and insulin-deficient rats, followed by a chase of unlabeled leucine after 30 min. Blood samples were collected at intervals over 24 h and the apolipoprotein components were separated by two-dimensional electrophoresis. The relative specific activities of sialylated isoforms of apo E were less than the relative specific activities of non-sialylated apo E isoforms. In contrast, sialylated isoforms of apo C-III had higher relative specific activities than non-sialylated apo C-III. No interconversions of apo E or apo C-III isoforms were found within the lipoprotein fractions. In insulin-deficient diabetic rats the relative specific activities of sialylated apo E and apo C-III isoforms were both increased relative to non-sialylated isoforms when compared with control rats. The results of this study suggest that the isoforms of apo E and apo C-III associated with the plasma lipoproteins of diabetic rats are changed in parallel with changes in synthesis of the isoforms. The changes in association with the isoforms of the apolipoproteins possibly contribute to abnormal metabolism of plasma lipoproteins in insulin deficiency.