The Effect of Aspartates on the Lipid and Carbohydrate Metabolism in Diabetics

1. In vitro incorporation of acetate-1-C¹⁴ into fatty acids by whole blood from diabetics is suppressed when compared to that of healthy controls. C¹⁴ incorporation into palmitate myristate, probably derived from malonyl CoA pathway, is greatly suppressed and that into 18- and 20 carbon fatty acids, formed via mitochondrial pathway, is relatively less suppressed.<br>2. As oxaloacetate added in diabetic whole blood corrected the above abnormalities in vitro, aspartates and the amino-derivatives of oxaloacetate were examined both in vitro and in vivo.<br>3. In vitro, L-monopotassium aspartate (abbreviated as K-asp) and L-magnesium aspartate (Mg-asp) selectively increased the C¹⁴ incorporation by healthy whole blood into palmitate at the concentrations of 10^-2, 10^-3 and 10^-4 Mol/Liter. Increased C¹⁴ incorporation into a fatty acid group 14:0+16:0, namely the increased activity of malonyl CoA pathway was observed by the addition of either 10^-2 to 10^-4 Mol/L K-asp or 10^-3 Mol/L Mg asp. The maximal stimulation of the pathway was brought up by K-asp at 10^-3 Mol/L concentration.<br>4. The patterns of C¹⁴ incorporation into fatty acids by whole blood from 6 diabetics were compared before and after 6 week administration of aspartates as the mixture of K-and Mg-asp in equal weight. The aspartates at the daily doses of 8.7, 18.8 and 20.3 mg/kg body weight increased C¹⁴ incorporation into total fatty acids; the C¹⁴ incorporation via not only malonyl CoA pathway but also mitochondrial pathway was stimulated. The maximal stimulation of malonyl CoA pathway was obtained at the dose of 20.3 mg/kg body weight /day. At the doses over 20.3 mg C¹⁴ incorporation into oleate was selectively increased inspite of the decreased incorporation into the other fatty acids; C¹⁴ incorporation into total fatty acids was significantly suppressed. C¹⁴ inc rporation into sterols was increased at the doses ranging from 8.7 to 28.3 mg/kg body weight per day and was decreased at the doses over 28.3 mg.<br>5. After the above period of the aspartate administration to the diabetics the serumm levels of total lipids, total fatty acids, phospholipids, total cholesterol, esterized and free cholesterols and triglycerides showed the trend toward decrease. There was no relationship between the trend and the aspartate doses. On the other hand, the percent composition of arachidonic acid to total fatty acids in whole blood was increased with a statistic significance.6. After aspartate administration to 19 diabetic patients at the daily doses ranging from 6 to 45 mg per kg dody weight for 3 to 6 months, the moderate improvement of their glucose tolerance was observed in 9 cases (47.4%). Medium and remarkable improvement were seen in 2 cases (10.5%) respectively. The improvement was predominantly seen in those patients with either ideal body weight or less than 150 mg fasting blood sugar or more than 7 years of diabetic history.