LIPOPROTEIN ALTERATIONS IN 10-WEEK-OLD AND 20-WEEK-OLD ZUCKER DIABETIC FATTY RATS - HYPERINSULINEMIC VERSUS INSULINOPENIC HYPERGLYCEMIA

Lipoprotein and apolipoprotein parameters were studied in the male Zuc ker diabetic fatty (ZDF) rat at 10 and 20 weeks of age, corresponding to hyperinsulinemic and insulinopenic type 2 diabetes mellitus, respec tively. At both ages, ZDF rats had elevated serum triglycerides, free fatty acids, and corticosterone, whereas 20-week ZDF rats had reduced thyroid hormones. At 10 weeks, the hyperlipidemia was confined to elev ations in pre-P triglyceride-rich (d < 1.006 g/mL) lipoproteins. By 20 weeks, all lipoprotein density fractions were increased compared with lean rats, with substantial increases in both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. In ZDF rats, th ere was a progressive increase in apolipoprotein B (apo B) from 1.0 ti mes control at 10 weeks to three times control at 20 weeks. The increa se in apo B was accompanied by a shift of apo B, particularly B100, fr om very-low-density lipoprotein (VLDL) into denser lipoproteins corres ponding to intermediate-density lipoproteins plus LDLs (1.006 < d < 1. 063 g/mL). In Zucker and 10-week ZDF rats, in the presence of hyperins ulinemia, the increase in serum apo B was predominantly apo B48 presen t in VLDL. By 20 weeks, when ZDF rats are insulinopenic, the mass rati o of B48:B100 shifted from 2.7 to 0.7. The shift was associated with a decrease in hepatic-edited apo B mRNA. Apo E increased in lean rats b etween 10 and 20 weeks of age. Although apo E also increased in ZDF ra ts, the increase by 20 weeks was less than that of lean rats. The mola r ratio of apo E to B in VLDL was decreased in ZDF rats. In lean rats, greater than 50% of apo E was present in HDL, in contrast to ZDF rats , where less than 20% of apo E was present in HDL. VLDL apo E shifted to denser fractions by 20 weeks of age, similar to apo B, The apo C le vel was more than double compared with the level in lean rats and was redistributed from the HDL fraction to lipoprotein fractions containin g apo B. Both apo A-I and apo A-IV levels more than doubled between 10 and 20 weeks in ZDF rats. The ZDF rat model may be useful in comparat ive studies of lipoproteins during diabetic progression from hyperinsu linemia to insulinopenia. Copyright (C) 1998 by W.B. Saunders