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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a hospital-based study in northwestern Ethiopia some clinical and biochemical features of diabetes mellitus have been assessed to contribute to the problem of classification of diabetes in a tropical country. Diabetes requiring primary insulin treatment is presented by unequivocally elevated blood glucose levels and the classic symptoms of the disease. Newly discovered cases and readmitted rural diabetics show significantly lower body mass indices and 31% have been classified as underweight. The overall frequency of ketonuria at (re)admission was 45% together with moderately elevated or high 3-hydroxybutyrate serum concentrations. The hormonal status is characterized by a reduced beta-cell function. Serum concentrations of all carnitine fractions are lower in both normal and diabetic Ethiopians when compared with Caucasoids. Carnitine precursor amino acids are normal and the complete amino acid spectrum reveales no clear-cut pattern related to protein-energy malnutrition.
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PMID:Ketosis, serum carnitine and its precursor amino acids in normal and diabetic ethiopians. 311 80

The main function of carnitine is the transport of fatty acids across the inner mitochondrial membrane to the side of beta-oxidation. In healthy subjects no carnitine deficiency occurs. There are many inborn errors with carnitine deficiency as a primary genetic defect or secondary to other familial disorders of metabolism. Furthermore some acquired diseases are associated with secondary carnitine deficiency. Myopathic and systemic forms of carnitine deficiency have been described. Most of the carnitine deficiency syndromes leading frequently to sudden death without therapy, are treatable with L-carnitine. A beneficial influence of L-carnitine to certain hyperlipoproteinemias, hyperlipidaemic diabetes mellitus and other diseases has been reported too.
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PMID:[Carnitine deficiency and carnitine therapy]. 328 80

Carnitine (beta-hydroxy-gamma-N-trimethylaminobutyric acid) is required for transport of long-chain fatty acids into the inner mitochondrial compartment for beta-oxidation. Widely distributed in foods from animal, but not plant, sources, carnitine is also synthesized endogenously from two essential amino acids, lysine and methionine. Human skeletal and cardiac muscles contain relatively high carnitine concentrations which they receive from the plasma, since they are incapable of carnitine biosynthesis themselves. Since the discovery of a primary genetic carnitine deficiency syndrome in 1973, carnitine has become the subject of extensive research. It is now recognized that carnitine deficiency may also occur secondary to genetic disorders of intermediary metabolism as well as to a variety of clinical disorders, including renal disease treated by hemodialysis, the renal Fanconi syndrome, cirrhosis, untreated diabetes mellitus, malnutrition, Reye's syndrome, and certain disorders of the endocrine, neuromuscular, and reproductive systems. Administration of the anticonvulsant valproic acid and total parenteral nutrition may also induce hypocarnitinemia. In many instances, the physiological implications of secondary carnitine deficiency have not been resolved. However, evidence for a specific carnitine requirement for the newborn, especially if preterm, is accumulating. Moreover, carnitine administration may have a favorable effect on some forms of hyperlipoproteinemia. Carnitine, now recognized as a conditionally essential nutrient, is a significant factor in preventive medicine.
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PMID:Carnitine: an overview of its role in preventive medicine. 353 87

The effects of streptozotocin-induced diabetes and the subsequent treatment of diabetic animals with insulin were studied using a dose of streptozotocin that produces highly ketotic animals 48 h after injection. Carnitine palmitoyltransferase of diabetic animals had apparent Ki values for malonyl-CoA that were approximately 10 times greater than control animals, indicating a greatly decreased affinity for malonyl-CoA in the diabetic state. Subsequent treatment of diabetic animals with insulin for 5 days produced non-ketotic animals with normal blood glucose, and the affinity of carnitine palmitoyltransferase for malonyl-CoA was increased to the control level. Treatment of other groups of ketotic diabetic animals with insulin produced substantial changes in the carnitine palmitoyltransferase apparent Ki value for malonyl-CoA within 4 h. These results suggest that insulin modulates the ketotic state, at least in part, by increasing the affinity of carnitine palmitoyltransferase for malonyl-CoA to bring about inhibition of fatty acid oxidation and ketogenesis.
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PMID:Alteration of the apparent Ki of carnitine palmitoyltransferase for malonyl-CoA by the diabetic state and reversal by insulin. 389 56

1. In an attempt to define the importance of acetate as a metabolic precursor, the activities of acetyl-CoA synthetase (EC 6.2.1.1) and acetyl-CoA hydrolase (Ec 3.1.2.1) were assayed in tissues from rats and sheep. In addition, the concentrations of acetate in blood and liver were measured, as well as the rates of acetate production by tissue slices and mitochondrial fractions of these tissues. 2. Acetyl-CoA synthetase occurs at high activities in heart and kidney cortex of both species as well as in rat liver and the sheep masseter muscle. The enzyme is mostly in the cytosol fraction of liver, whereas it is associated with the mitochondrial fraction in heart tissue. Both mitochondrial and cytosol activities have a K(m) for acetate of 0.3mm. Acetyl-CoA synthetase activity in liver was not altered by changes in diet, age or alloxan-diabetes. 3. Acetyl-CoA hydrolase is widely distributed in rat and sheep tissues, the highest activity being found in liver. Essentially all of the activity in liver and heart is localized in the mitochondrial fraction. Hepatic acetyl-CoA hydrolase activity is increased by starvation in rats and sheep and during the suckling period in young rats. 4. The concentrations of acetate in blood are decreased by starvation and increased by alloxan-diabetes in both species. The uptake of acetate by the sheep hind limb is proportional to the arterial concentration of acetate, except in alloxan-treated animals, where uptake is impaired. 5. Acetate is produced by liver and heart slices and also by heart mitochondrial fractions that are incubated with either pyruvate or palmitoyl-(-)-carnitine. Liver mitochondrial fractions do not form acetate from either substrate but instead convert acetate into acetoacetate. 6. We propose that acetate in the blood of rats or starved sheep is derived from the hydrolysis of acetyl-CoA. Release of acetate from tissues would occur under conditions when the function of the tricarboxylic acid cycle is restricted, so that the circulating acetate serves to redistribute oxidizable substrate throughout the body. This function is analogous to that served by ketone bodies.
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PMID:Production and utilization of acetate in mammals. 444 81

1. The total acid-soluble carnitine concentrations of four tissues from Merino sheep showed a wide variation not reported for other species. The concentrations were 134, 538, 3510 and 12900nmol/g wet wt. for liver, kidney cortex, heart and skeletal muscle (M. biceps femoris) respectively. 2. The concentration of acetyl-CoA was approximately equal to the concentration of free CoA in all four tissues and the concentration of acid-soluble CoA (free CoA plus acetyl-CoA) decreased in the order liver>kidney cortex>heart>skeletal muscle. 3. The total amount of acid-soluble carnitine in skeletal muscle of lambs was 40% of that in the adult sheep, whereas the concentration of acid-soluble CoA was 2.5 times as much. A similar inverse relationship between carnitine and CoA concentrations was observed when different muscles in the adult sheep were compared. 4. Carnitine was confined to the cytosol in all four tissues examined, whereas CoA was equally distributed between the mitochondria and cytosol in liver, approx. 25% was present in the cytosol in kidney cortex and virtually none in this fraction in heart and skeletal muscle. 5. Carnitine acetyltransferase (EC 2.3.1.7) was confined to the mitochondria in all four tissues and at least 90% of the activity was latent. 6. Acetate thiokinase (EC 6.2.1.1) was predominantly (90%) present in the cytosol in liver, but less than 10% was present in this fraction in heart and skeletal muscle. 7. In alloxan-diabetes, the concentration of acetylcarnitine was increased in all four tissues examined, but the total acid-soluble carnitine concentration was increased sevenfold in the liver and twofold in kidney cortex. 8. The concentration of acetyl-CoA was approximately equal to that of free CoA in the four tissues of the alloxan diabetic sheep, but the concentration of acid-soluble CoA in liver increased approximately twofold in alloxan-diabetes. 9. The relationship between CoA and carnitine and the role of carnitine acetyltransferase in the various tissues is discussed. The quantitative importance of carnitine in ruminant metabolism is also emphasized.
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PMID:Relationships between carnitine and coenzyme A esters in tissues of normal and alloxan-diabetic sheep. 507 38

The effects of L-carnitine administration on the severity of diabetes were investigated. Serum glucose, free fatty acids (FFA), triglycerides, and ketones from diabetic and normal rats injected for 2 weeks with 3 g/kg/d of either L-carnitine or saline were assayed. Hearts were analyzed for carnitine and long-chain acyl coenzyme A. L-carnitine treatment to diabetic rats significantly reduced serum glucose, FFA, triglycerides, and ketones. In nondiabetic rats, carnitine increased serum ketones while FFA and triglycerides were decreased. L-carnitine treatment to diabetic rats prevented a decrease in myocardial total carnitine content. Long-chain acyl carnitine increased while long-chain acyl coenzyme A decreased. In another experiment, L-carnitine administration (750 mg/kg/d for 14 days) significantly improved the recovery of cardiac output after 60, 90, and 120 minutes of ischemia in diabetic perfused hearts. These results suggest that L-carnitine therapy may reduce the severity of diabetes mellitus and improve myocardial performance.
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PMID:Improvement of myocardial function in diabetic rats after treatment with L-carnitine. 670 20

The effects of substrates, fasting, and diabetes on carnitine transport into the myocardial cells were characterized in perfused adult rat hearts. Increasing the level of acetyl carnitine and decreasing the level of free carnitine by perfusion with various substrates did not alter the rate of carnitine transport. Carnitine transport was enhanced by the perfusion with palmitate. At low work, addition of 1.2 mM palmitate increased carnitine transport by 33%, whereas high work + 1.2 mM palmitate stimulated transport 60% over that of glucose-perfused hearts. The enhancement of carnitine transport correlated with a rise in tissue levels of long-chain acyl carnitine. When the level of long-chain acyl carnitine was increased prior to measurement of carnitine transport, the enhancement of uptake seen with palmitate as substrate was not observed. Carnitine transport in hearts from 48-h-fasted or diabetic animals was not different from transport in hearts of fed animals. Diabetes resulted in decreased tissue levels of carnitine. The decrease was observed after 48 h of severe diabetes and after several weeks of mild diabetes. In each case, low tissue levels of carnitine were associated with reduced serum carnitine. Serum carnitine decreased to a value near the Km for carnitine transport in diabetic animals. It is concluded that a decreased rate of transport due to lower serum carnitine may be responsible for reduced levels of carnitine seen in diabetic hearts.
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PMID:A mechanism for reduced myocardial carnitine levels in diabetic animals. 711 26

L-Carnitine is essential for the transport of long chain fatty acids into mitochondria and, hence, in ketoacid production. Total, free and acylcarnitine in plasma and urine have been determined in 52 children and adolescents with insulin-dependent juvenile diabetes and compared with 72 controls. The subjects were divided into three age groups 8-10, 11-15 and 16-20 years. The plasma, total and free carnitine were significantly lower in diabetic patients than in controls in all age groups. Acylcarnitine was significantly higher in the diabetic patients than in the controls in the two younger age groups. No sex-related differences in plasma carnitine and its derivatives were found in the two younger groups. A statistically significant correlation coefficient was noted between glycosylated hemoglobin and the plasma acyl/free carnitine ratio, 2 p less than 0.05. The daily urinary excretion and renal clearance of carnitine and its derivatives showed few significant differences between the diabetic and the control subjects.
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PMID:Plasma and urine carnitine in children with diabetes mellitus. 713 62

L-carnitine is essential for the transport of long-chain fatty acids into mitochondria and their oxidation. Recently, a relationship between plasma free fatty acids (FFA) and L-carnitine metabolism has been observed. Plasma free L-carnitine (FC), FFA, triglycerides, cholesterol, blood glucose concentration and daily excretion of FC were determined in 20 diabetic patients as well as in 18 control subjects. Both in male diabetics and in male controls, plasma FC was significantly higher than in females. Mean plasma FC was found to be significantly reduced in diabetics (21 +/- 2 vs 35 +/- 2 mumol/1 in non-diabetic subjects; p less than 0.005). Daily urinary excretion of FC was clearly lower in diabetic patients than in controls (172 +/- 34 vs 403 +/- 38 mumol/24 h; p less than 0.001). The reduced plasma FC in diabetes mellitus may be due to redistribution between circulating free and esterified carnitine and to increased utilization of FC for synthesis of acylcarnitine in tissues.
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PMID:Plasma and urine free L-carnitine in human diabetes mellitus. 721 Oct 90


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