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Biomedical subjects

D W Foster

Publications and source records attributed to D W Foster.

At least 91 records · Page 5Linked to original sources
PubMed1976

An improved and simplified radioisotopic assay for the determination of free and esterified carnitine.

The radioisotopic assay for carnitine first described by Cederblad and Lindstedt (Clin. Chim. Acta. 37:235-543, 1972) and modified by Bohmer et al (Clin. Chim. Acta. 57:55-61, 1974) has been improved and simplified. As a result, the assay yields a linear response over a wide range of carnitine concentrations without the need for excessive amounts of labeled acetyl-CoA. In addition, it will measure very small quantities of carnitine even in the presence of excess acylcarnitine. The method allows rapid determination of free and esterified carnitine in small volumes of plasma (50 mul is sufficient) without the need for prior deproteinization of the samples.

Carbon Radioisotopes↗
PubMed1975

Role of carnitine in hepatic ketogenesis.

The enhancement of long-chain fatty acid oxidation and ketogenesis in the perfused rat liver, whether induced acutely by treatment of fed animals with anti-insulin serum or glucagon, or over the longer term by starvation or the induction of alloxan diabetes, was found to ba accompanied by a proportional elevation in the tissue carnitine content. Moreover, when added to the medium perfusing livers from fed rats, carnitine stimulated ketogenesis from oleic acid. The findings suggest that the increased fatty acid flux through the carnitine acyltransferase (carnitine palmitoyl-transferase; palmitoyl-CoA:L-carnitine O-palmitoyltransferase; EC 2.3.1.21) reaction brought about by glucagon excess, with or without insulin deficiency, is mediated, at least in part, by elevation in the liver carnitine concentration.

Animals↗
PubMed1975

Hormonal control of ketogenesis. Rapid activation of hepatic ketogenic capacity in fed rats by anti-insulin serum and glucagon.

The enhanced capacity for long-chain fatty acid oxidation and ketogenesis that develops in the rat liver between 6 and 9 h after the onset of starvation was shown to be inducible much more rapidly by administration of anti-insulin serum or glucagon to fed rats. After only 1 h of treatment with either agent, the liver had clearly switched from a "nonketogenic" to a "ketogenic" profile, as determined by rates of acetoacetate and b-hydroxybutyrate production on perfusion with oleic acid. As was the case after starvation, the administration of insulin antibodies or glucagon resulted in depletion of hepatic glycogen stores and a proportional increase in the ability of the liver to oxidize long-chain fatty acids and (-)-octanoylcarnitine, suggesting that all three treatment schedules activated the carnitine acyltransferase system of enzymes. In contrast to anti-insulin serum, which produced marked elevations in plasma glucose, free fatty acid, and ketone body concentrations, glucagon treatment had little effect on any of these parameters, presumably due to enhanced insulin secretion after the initial stimulation of glycogenolysis. Thus, after treatment with glucagon alone, it was possible to obtain a "ketogenic" liver from a nonketotic animal. The results are consistent with the possibility that the activity of carnitine acyltransferase, and thus ketogenic capacity, is subject to bihormonal control through the relative blood concentrations of insulin and glucagon, as also appears to be the case with hepatic carbohydrate metabolism.

Animals↗
PubMed1973

Acute reversal of experimental diabetic ketoacidosis in the rat with (+)-decanoylcarnitine.

The effect of (+)-decanoylcarnitine, a potent inhibitor of long-chain acylcarnitine transferase, was tested for its ability to inhibit hepatic ketogenesis both in the isolated perfused liver and in vivo in severely ketotic alloxan diabetic rats. In vitro the inhibitor caused an almost complete block in ketone body production. In vivo (+)-decanoylcarnitine caused a rapid reversal of ketosis under conditions where large doses of insulin had little effect. A combination of the two agents produced an even more striking fall in plasma ketone levels.While (+)-decanoylcarnitine alone had no effect on plasma glucose levels it enhanced the hypoglycemic effect of insulin in anesthetized animals. Loss of this effect was noted in nonanesthetized animals, possibly as a result of increased muscle activity. Studies in the isolated perfused liver indicated that the blockade of fatty acid oxidation and ketogenesis produced by (+)-decanoylcarnitine was rapidly reversible upon removal of the inhibitor.

Animals↗
PubMed1972

Studies of the development of diabetic ketosis in the rat.

Plasma glucose, free fatty acid, ketone, and triglyceride concentrations were measured at frequent intervals after the administration of alloxan to rats. Hepatic triglyceride levels were determined in the same animals. During the second 24-hr period after alloxan administration, severe ketoacidosis developed and triglyceride concentrations in the liver became markedly elevated. This finding was incompatible with the thesis that enhanced ketogenesis under circumstances of increased free fatty acid delivery to the liver requires diminished triglyceride synthesis. Plasma insulin and glucagon concentrations were determined at each time point. Initial changes in plasma glucose, ketones, free fatty acids, and triglycerides were accompanied by a fall in insulin concentrations, but no change occurred in glucagon levels. However, concentrations of the latter hormone increased dramatically in the second 24 hr after alloxan treatment and probably contributed to the development of the extreme hyperglycemia observed during this time period.

Acetates↗