CORRELATION OF INSULIN DEFICIENCY AND HYPERTRIGLYCERIDEMIA IN DIABETIC RATS

The relationship between plasma insulin (IRI) and lipid concentration, or triglyceride (TG) kinetics was studied in streptozotocin-induced diabetic rats (DM) to examine how insulin deficiency is associated with the mechanism of hypertriglyceridemia (HTG) in diabetes. Plasma glucose and ketones were significantly elevated and IRI reduced in DM. Plasma glucagon concentration in DM was similar to controls. The plasma concentration of TG, total cholesterol, phospholipid and apoprotein B was 3-4-fold higher in DM compared to control rats. The HTG in DM was mainly attributable to an increase in the concentration of TG-rich lipoprotein (TRL). Multiple linear regression analysis showed a positive relationship between the concentration of non-esterified fatty acid and plasma lipids, but the decrease in IRI best correlated with increased concentrations of lipids and apoprotein B in plasma and TRL. Neither glucose nor glucagon correlated significantly with lipids or apoprotein B concentration in plasma or TRL. The rate of entry of TG into blood was similar between DM and controls, and in DM this significantly correlated with IRI. Clearance of radiolabeled TRL-TG in DM was significantly decreased and correlated with IRI. Conversely, the removal of radiolabeled Intralipid-TG was similar for DM and controls. The data suggest that insulin critically regulates TRL-TG metabolism in DM and that a catabolic defect of TRL-TG due to insulin deficiency is a main reason for the HTG. The discrepancy of fractional catabolic rate (FCR) between TRL and Intralipid suggests that hydrolysis of TG by lipoprotein lipase is not severely impaired, but a direct removal process of TRL is impaired in diabetes and that insulin may regulate this.