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Biomedical subjects

S A McCune

Publications and source records attributed to S A McCune.

51 records · Page 3Linked to original sources
PubMed1984

Inhibition of fatty acid synthesis in isolated adipocytes by 5-(tetradecyloxy)-2-furoic acid.

The compound 5-(tetradecyloxy)-2-furoic acid (TOFA), a hypolipidemic agent, inhibits fatty acid synthesis, lactate and pyruvate accumulation and CO2 release in isolated rat adipocytes. TOFA stimulates the accumulation of citrate. ATP levels are not lowered by TOFA. In comparison with the natural fatty acid, oleate, TOFA exhibited a much greater inhibitory effect on lipogenesis. TOFyl-CoA formation within intact adipocytes was demonstrated. Although not inhibited by TOFA, acetyl-CoA carboxylase is inhibited by TOFyl-CoA. It is proposed that many of the metabolic effects of TOFA in isolated adipocytes can be explained by TOFyl-CoA inhibition of acetyl-CoA carboxylase. TOFA inhibits glycolysis as a secondary event with the primary event of inhibition of fatty acid synthesis causing an accumulation of citrate which is an inhibitor of phosphofructokinase.

Acyl Coenzyme A↗
PubMed1984

Age-related decrease in sensitivity to glucagon and dibutyryl cyclic AMP inhibition of fatty acid synthesis in hepatocytes isolated from obese female Zucker rats.

Hepatocytes were isolated from 3 and 5 month old female genetically obese Zucker rats and their lean littermate controls. An age-dependent loss in sensitivity of fatty acid synthesis to inhibition by both glucagon and dibutyryl cyclic AMP was observed with hepatocytes from the obese rats. Hepatocytes from lean animals were much more sensitive to these agents, regardless of age. Low concentrations of glucagon and dibutyryl cyclic AMP actually produced some stimulation of fatty acid synthesis with hepatocytes prepared from the older obese rats. 5-Tetradecyloxy-2-furoic acid, a compound which inhibits fatty acid synthesis, was a very effective inhibitor of fatty acid synthesis by hepatocytes isolated from all rats used in the study. An inhibition of lactate plus pyruvate accumulation and a strong stimulation of glycogenolysis occurred in response to both glucagon and dibutyryl cyclic AMP with hepatocytes from both age groups of lean and obese rats. The results suggest that with aging of the obese female Zucker rat some step of hepatic fatty acid synthesis becomes progressively less sensitive to inhibition by glucagon and dibutyryl cyclic AMP. This may play an important role in maintenance of obesity in these animals.

Aging↗
PubMed1981

Comparative studies on fatty acid synthesis, glycogen metabolism, and gluconeogenesis by hepatocytes isolated from lean and obese Zucker rats.

Hepatocytes isolated from genetically obese female Zucker rats and lean female Zucker rats were compared. Hepatocytes from fed obese rats exhibited greater rates of fatty acid synthesis, more extensive accumulation of lactate and pyruvate from their glycogen stores, increased rates of net glucose utilization but produced less ketone bodies from exogenous fatty acids and had lower citrate levels than hepatocytes from lean rats. Lipogenesis was not as sensitive to dibutyryl cyclic AMP (DBcAMP) inhibition in hepatocytes from obese rats but glycogenolysis was stimulated to the same extent by this nucleotide in both preparations. Ketogenesis was less sensitive to stimulation by DBcAMP in hepatocytes from obese rats. A difference in sensitivity of lipogenesis to DBcAMP was not found when lactate plus pyruvate was added to the incubation medium, suggesting that a greater rate of glycolysis by hepatocytes from obese rats accounts for their relative insensitivity to DBcAMP. Citrate levels were elevated by DBcAMP to a greater extent in hepatocytes from obese rats. Hepatocytes prepared from lean rats starved for 48 hr were glycogen depleted and lacked significant capacity for lipogenesis and glycogen synthesis. In contrast, hepatocytes isolated from starved obese rats retained considerable amounts of liver glycogen and exhibited detectable rates of lipogenesis and glycogen synthesis. Hepatocytes prepared from starved lean rats gave faster apparent rates of lactate gluconeogenesis than hepatocytes prepared from starved obese rats. Thus, hepatocytes prepared from obese Zucker rats are more glycogenic, glycolytic, and lipogenic but less ketogenic and glucogenic than hepatocytes prepared from lean rats.

Animals↗
PubMed1979

Neoplastic transformation-linked alterations in arginyl-tRNA synthetase activity.

The behavior of the activity of arginyl-tRNA synthetase (L-arginine : tRNAArg Ligase(AMP-forming), EC 6.1.1.19) was determined in extracts of rat liver: normal adult, normal proliferating (from developing and from partially hepatectomized rats), and neoplastic (hepatomas of different growth rates) and in extracts of rat kidney cortex and transplantable kidney tumors. The Km values for arginine, ATP, and tRNA of the enzyme of the rapidly growing hepatoma 3924A were the same as those of the enzyme from the liver of control rats. The pH optima of the control and neoplastic livers were in the same range of 7.25-8.0. Taking the hepatic specific activity for arginyl-tRNA synthetase as 100%, deep layer of gut, thymus and testis had higher activity; renal cortex and spleen had the same activity; and skeletal muscle, brain, heart, lung, superficial layer of gut and adipose tissue had lower activity. In a wide spectrum of hepatomas of different growth rates, a significant increase of 1.4-2.4-fold in arginyl-tRNA synthetase activity was observed when compared with that of liver of control normal rats. This elevation in enzyme activity in hepatomas appears to be specific to neoplasia, since it is unaltered in regenerating and low in differentiating liver. The increase in arginyl-tRNA synthetase in the liver tumors appears to be transformation-linked, since the activity was increased in all hepatomas, even in the slowest growing ones. Furthermore, the increase in enzyme activity was not limited to hepatic neoplasms, since a rise was also observed in transplantable rat kidney tumors. Thus, the reprogramming of gene expression in neoplastic tissue entails an increase in arginine-tRNA synthetase activity.

Aging↗
PubMed1979

Inhibition of hepatic lipogenesis by 2-tetradecylglycidic acid.

2-Tetradecylglycidic acid (TDGA), a hypoglycemic agent, has been found to be a very effective inhibitor of de novo fatty acid synthesis by isolated hepatocytes. A comparison was made between the effectiveness of TDGA and 5-(tetradecyloxy)-2-furoic acid (TOFA), a hypolipidemic agent, on the metabolic processes of isolated hepatocytes. These compounds are structurally related and both inhibit fatty acid synthesis; however, they have opposite effects from each other on the oxidation and esterification of fatty acids. TDGA inhibits whereas TOFA stimulates fatty acid oxidation. TDGA stimulates whereas TOFA inhibits fatty acid esterification.

Animals↗
PubMed1977

A genetic study of erythrocyte arginine-tRNA synthetase activity in man.

To search for evidence of genetic variation among the aminoacyl-tRNA synthetases, a semi-automated assay procedure employing a Technicon AutoAnalyzer was used to measure erythrocyte arginine-tRNA synthetase activity in samples obtained from normal human twins of various ages. Variation in enzyme activity within the older DZ twins was five times that of the MZ twins suggesting the existence of genetically determined variation in enzyme activity. Higher enzyme activity was observed in newborn DZ unlike-sexed twins than in like-sexed twins for either zygosity. Possible explanations for this observation are discussed.

Adolescent↗
PubMedDate not supplied

Insulin-like growth factor mRNA expression in tissues of lean and obese male SHFF/Mcc-fa(cp) rats.

No differences were detected in serum IGF-I levels between lean and obese male SHFF/Mcc-fa(cp) rats expressing non-insulin-dependent diabetes mellitus (NIDDM). In contrast, serum insulin levels, and blood glucose levels were significantly elevated in obese as compared to lean littermates (P < 0.05), indicating that the obese animals were diabetic. Northern blot analysis of total tissue RNA using labeled cDNAs for IGF-I and IGF-II revealed a decrease in liver and adipose IGF-I mRNA expression in the obese littermates while IGF-II mRNA expression was decreased only in adipose tissue of obese animals as compared to lean littermates.

Adipose Tissue↗
PubMedDate not supplied

Cardiovascular disease in genotypes for obesity and diabetes.

Cardiovascular diseases represent a major cause of morbidity and mortality in both obese and diabetic patients. The mechanisms by which diabetes or obesity cause the cardiac lesions is poorly understood. A number of risk factors associated with the development of atherosclerotic vascular disease, a precursor of heart disease, are found in diabetes and obesity. There is evidence that diabetes or obesity may even cause a primary cardiomyopathy. The use of animal models with obesity or diabetes with various combinations of risk factors may clarify what each component contributes to the expression of cardiovascular disease. This report summarizes some of the current information on the cardiovascular complications found in various animal models of obesity and diabetes.

Animals↗