Effect of chronic glucagon administration on lipoprotein composition in normally fed, fasted and cholesterol-fed rats.

Male adult Wistar rats received daily (at 9 a.m. and 5 p.m.) 10 micrograms of zinc-protamine glucagon by subcutaneous injection for 8 days. Plasma cholesterol levels were decreased by 36% in fed rats, 33% in cholesterol-fed rats and by 55% in fasted rats. Lipoproteins were separated into 22 fractions by ultracentrifugation using a density gradient. Glucagon administration decreased the cholesterol content in all lipoproteins except low density lipoprotein (LDL1) (1.006-1.040) and very low density lipoprotein (VLDL) from cholesterol-fed rats. The main decrease (-57 to -81%) was observed in 1.050-1.100 g/mL lipoproteins (LDL2 and HDL2), which contained a large amount of apo E, while HDL3 cholesterol was not affected. Triacylglycerol levels were decreased only in chylomicrons and VLDL (-70%) of fed and cholesterol-fed rats, while plasma and lipoprotein triacylglycerol levels were not changed in fasted rats treated with glucagon. In normally fed rats glucagon administration increased by 42% the fractional catabolic rate of [125I]HDL2 while the absolute catabolic rate appeared to be unchanged. Glucagon seems to be a potent hypolipidemic agent affecting mainly the apo E-rich lipoproteins. Its chronic administration limits lipoprotein accumulation which occurs upon cholesterol feeding.

Effect of chronic glucagon administration on the metabolism of triacylglycerol-rich lipoproteins in rats fed a high sucrose diet.

Male adult Wistar rats were fed a semipurified diet rich in sucrose (53 g/100 g diet). The effects of chronic glucagon administration (20 micrograms.day-1.rat-1, for 21 d) were studied on plasma lipid levels, triacylglycerol secretion rates and fractional catabolic rates determined by the intravenous fat tolerance test. Triacylglycerol secretion rates of plasma, chylomicron and very low density lipoprotein (VLDL) were measured by using the Triton WR 1339 method. In both fasting and postprandial states, the different rates were not significantly modified by glucagon treatment. However, in the treated animals, significantly decreased triacylglycerol concentrations were observed in plasma and VLDL during fasting (-41 and -46%, respectively) and also in chylomicrons in the postprandial state (-37%) relative to control animals. These data could be accounted for by an increased removal rate of triacylglycerol-rich lipoprotein. The estimated values of fractional rate constants (Triton WR 1339 experiment) were increased for VLDL (+62%) in the fasting state and for chylomicrons (+104%) in the postprandial state. Similarly, the fractional catabolic rate determined with the intravenous fat tolerance test (Intralipid, Kabivitrum, Sweden) was increased 49% by glucagon treatment, suggesting an effect of glucagon on the catabolism of triacylglycerol-rich lipoproteins. Glucagon treatment did not modify the composition of VLDL obtained 60 min after Triton WR 1339 injection, except that in the fasting state apo B100 proportions and concentrations increased, suggesting a specific effect on the hepatic secretion of apo B100 VLDL.

Lipolytic activities in rats fed a sucrose-rich diet supplemented with either cystine or cholesterol: relationships with lipoprotein profiles.

To study the relationships between lipolytic activities and plasma lipoprotein levels in rats, three diets were given for 8 weeks: a semipurified diet (based on sucrose, casein and lard) and this diet enriched with 5% cystine or with 1% cholesterol. Both supplemented diets induced hypercholesterolemia. Lipoprotein analysis by density gradient ultracentrifugation of plasma indicated that hypercholesterolemia of cystine-fed rats (+52%) was characterized by an increased cholesterol level in high-density lipoprotein (HDL; +131%) and low-density lipoprotein 2 (LDL2; +147%), the lipoprotein fraction containing essentially apolipoprotein-E-rich high-density lipoproteins (HDL1), and was associated with a decreased cholesterol level in triglyceride-rich lipoproteins (TRL: -69%). That obtained by cholesterol feeding (+28%) was due to a large increase in the TRL cholesterol level (+315%) whereas cholesterol was reduced in HDL (-40%) and in LDL2 (-60%). Under these dietary conditions, the activity of hepatic lipase (HL) was measured in liver homogenates and those of both HL and lipoprotein lipase were measured in plasma after heparin injection. The activity of HL (1,783 +/- 132 mU/g liver in control rats) was increased by 48% in cystine-fed rats and decreased by 40% in cholesterol-fed rats. Similar changes were observed in the activity of both lipases measured in postheparin plasma. Highly significant positive correlations linked each lipolytic activity with the level of cholesterol, phospholipids and proteins in LDL2 (HDL1-rich fraction) and in HDL. In contrast, significant negative correlations were found between all of the TRL components and the activity of the lipases.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chronic glucagon administration on rat lipoprotein composition.

Male adult rats of the Wistar strain received daily at 9 a.m. and 5 p.m. 10 micrograms of Zn-protamine glucagon (Novo) for 21 days by subcutaneous injections. Plasma levels of cholesterol, triacylglycerol and phospholipids were decreased by 47, 40 and 21%, respectively. Lipoproteins were separated by sequential ultracentrifugation. Concentrations of cholesterol, phospholipids and proteins were decreased in chylomicrons, VLDL, LDL2 (1.040-1.063 g/ml) and HDL, LDL2 being the most affected by glucagon treatment (-70%). Triacylglycerol levels were decreased only in chylomicrons and VLDL. The relative proportions of cholesterol, triacylglycerol, phospholipids and proteins in lipoproteins were virtually unchanged by glucagon, suggesting a reduced number of some lipoprotein particles in plasma. However, lipoproteins of glucagon-treated rats were depleted in cholesteryl esters, while the proportion of triacylglycerol increased in LDL and HDL. Apo E contents were decreased in plasma, LDL1 (1.006-1.040 g/ml), LDL2 and HDL, whereas apo B100 proportions increased in VLDL and LDL1 in glucagon-treated rats. Glucagon appeared to be a potent hypolipidemic agent affecting mainly the apo-E-rich lipoproteins.

Design of a chemiluminescent and bioluminescent photometer.

An apparatus for chemi- and bioluminescence measurements is described. The main features are in high sensitivity: for example, 5 10(-12) M adenosine triphosphate, 5 10(-7) M glucose, 2 10(-9) M perhydrol and 4 10(-13) M peroxidase are easily detected; its fast mixing time and the possibility of injecting a reactant, at any time, enabling kinetic studies. Moreover, its compactness and 12 V battery supply allow measurements outside of laboratories.