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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

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. 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 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

Carnitine facilitates fatty acid transport across mitochondrial membranes, playing a key role in fatty acid oxidation and ketogenesis. To investigate the mechanism by which carnitine and its esters are supplied to the fetus, we measured free carnitine (FC) and acyl carnitine (AC) in amniotic fluid during late pregnancy, and FC, AC and beta-hydroxybutyrate (beta-OHB) in maternal and fetal plasma at vaginal term delivery. Amniotic fluid AC levels were elevated in pregnancies complicated by toxemia and diabetes mellitus, possibly reflecting placental transfer during abnormal fat catabolism. Maternal plasma levels of beta-OHB and AC were elevated and positively correlated at vaginal delivery, indicating enhanced fatty acid utilization. The positive correlation between maternal and fetal FC, AC and beta-OHB plasma levels suggests placental transfer. The maternal-fetal concentration gradient was descending for beta-OHB and AC and ascending for FC. No umbilical venous-arterial gradient for AF and beta-OHB was found, suggesting that the fetus does not utilize substantial amounts of either substance. The results demonstrate that fetal FC and AC levels are influenced by changes in maternal fat metabolism.
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PMID:The influence of maternal fat metabolism on fetal carnitine levels. 726 87

Carnitine was determined radioenzymatically in the plasma of 415 hospital employees involved in a screening programme for prevention of major cardiovascular risks. A reference population (N = 340) was extracted after excluding subjects with hypertension, diabetes mellitus or treatment for hypercholesterolaemia. This population showed a Gaussian distribution for total and free carnitine concentrations both in females and males but not for acyl carnitine or the acyl/free ratio. Females had lower total and free carnitine concentrations but a higher ratio of acyl/free carnitine than males. These differences were not detectable in older subjects (35 years for the acyl/free ratio, 45 years for total and free carnitine concentrations). Females with a body mass index > 28 had a lower acyl/free ratio than their respective controls. The differences in carnitine concentrations indicate that sex and age should be matched in patients or experimental groups and controls in studies involving carnitine plasma concentrations.
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PMID:Plasma carnitines: reference values in an ambulatory population. 826 May 30

Defective metabolism of long-chain fatty acids and/or their accumulation in nerve may impair nerve function in diabetes by altering plasma or mitochondrial membrane integrity and perturbing intracellular metabolism and energy production. Carnitine and its acetylated derivatives such as acetyl-L-carnitine (ALC) promote fatty acid beta-oxidation in liver and prevent motor nerve conduction velocity (MNCV) slowing in diabetic rats. Neither the presence nor the possible implications of putative ALC deficiency have been definitively established in diabetic nerve. This study explored sciatic nerve ALC levels and the dose-dependent effects of ALC replacement on sciatic nerve metabolites, Na,K-ATPase, and MNCV after 2 and 4 weeks of streptozotocin-induced diabetes (STZ-D) in the rat. ALC treatment that increased nerve ALC levels delayed (to 4 weeks) but did not prevent nerve myo-inositol (MI) depletion, but prevented MNCV slowing and decreased ouabain-sensitive (but not -insensitive) ATPase activity in a dose-dependent fashion. However, ouabain-sensitive ATPase activity was also corrected by subtherapeutic doses of ALC that did not increase nerve ALC or affect MNCV. These data implicate nerve ALC depletion in diabetes as a factor contributing to alterations in nerve intermediary and energy metabolism and impulse conduction in diabetes, but suggest that these alterations may be differentially affected by various degrees of ALC depletion.
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PMID:Acetyl-L-carnitine deficiency as a cause of altered nerve myo-inositol content, Na,K-ATPase activity, and motor conduction velocity in the streptozotocin-diabetic rat. 869 23

A quantitative study of the effect of carnitine deficiency on expression of glycolytic and gluconeogenic enzymes was performed using juvenile visceral steatosis mice which are systemically deficient in carnitine. The amounts of glucokinase and L-type pyruvate kinase mRNA were reduced in homozygotes, compared to heterozygotes and normal controls at 2 and 8 weeks. Liver-type phosphofructokinase, however, did not differ significantly. The abundance of fructose 1,6-bisphosphatase mRNA was unchanged at 2 and 8 weeks. The level of phosphoenolpyruvate carboxykinase mRNA was increased slightly at 2 weeks, but not at 8 weeks. A part of these changes could not be explained by the plasma glucose or insulin level. Carnitine administration restored the mRNA of these enzymes to normal levels. These results suggest that carnitine deficiency affects the expression of these liver enzymes.
Diabetes Res Clin Pract 1996 May
PMID:Disordered expression of glycolytic and gluconeogenic liver enzymes of juvenile visceral steatosis mice with systemic carnitine deficiency. 885 99

Carnitine is present in the eye tissues of the rabbit and the highest concentration is found in the lens. In streptozotocin-diabetic rats, the carnitine loss of the lens is an initial and important event. At 8 days after the induction of diabetes, the carnitine content in the rat lens was reduced by 63% compared to control. The loss of lens carnitine continued at 15 and 45 days after the induction. Total carnitine level in the serum was diminished by 15 days, and the reduction in percentage term was much lower in comparison to the loss of lens carnitine. In the rabbit after alloxan-diabetes induction, there is an extensive loss of carnitine in the lens: -85% after 4 months. The carnitine levels in the other eye tissues seem substantially unaffected. The loss of lens carnitine was present even with an inconsistent hyperglycaemia. No difference was found in serum carnitine levels between controls and alloxan-treated rabbits. The role of carnitine in lens is still unclear, but its loss may be related to the appearance of cataract. A derivative of carnitine, acetylcarnitine, might prevent the processes involved in the formation of cataracts by a pharmacological action, as has been shown for aspirin.
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PMID:In experimental diabetes the decrease in the eye of lens carnitine levels is an early important and selective event. 917 53


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