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

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

L-Carnitine metabolism is abnormal in diabetes mellitus, and treatment with acetyl-L-carnitine (ALC) improves the function of cardiac muscle, retina, and peripheral nerve in experimental models. The aim was to compare the effects of ALC and proprionyl-L-carnitine (PLC) on motor and sensory nerve conduction in streptozotocin-diabetic rats and to ascertain whether their action could be mediated by a vascular mechanism. ALC and PLC treatment for 2 months after diabetes induction attenuated the development of sciatic motor nerve conduction velocity (NCV) deficits by 59.4% +/- 4.4% and 46.9% +/- 3.2%, respectively. There was a similar level of protection for sensory saphenous NCV (42.9% +/- 6.6% and 47.8% +/- 6.0%, respectively). Neither ALC nor PLC prevented the development of resistance to hypoxic conduction failure (RHCF) in sciatic nerve from diabetic rats. A 46.5% +/- 3.4% deficit in sciatic endoneurial blood flow, measured by microelectrode polarography and hydrogen clearance, in diabetic rats was partially prevented by both ALC (48.7% +/- 6.4%) and PLC (69.4% +/- 10.1%). ALC had no significant effect on blood flow in nondiabetic rats. Thus, the data show that these L-carnitine derivatives have a similar efficacy in preventing nerve dysfunction, which depends on a neurovascular action.
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PMID:Effects of acetyl- and proprionyl-L-carnitine on peripheral nerve function and vascular supply in experimental diabetes. 766 97

Serum concentration and urinary excretion of levocarnitine (L-carnitine, CAS 541-15-1) family components were evaluated in a Wistar derived strain of genetically diabetic rats BB/BB, in comparison with normal Wistar rats, and their control rats BB/WB of both sexes. BB/BB diabetic animals have lower serum concentration of total-L-carnitine (TC), L-carnitine (LC), acetyl-L-carnitine (ALC), and short chain L-carnitine esters (SCLCE) than both the strains of non-diabetic rats, as previously observed in streptozotocin diabetic rats. No or marginal variations between control and diabetic rats were detected in cumulative urinary excretion of L-carnitine family components. A strain difference was observed between Wistar and BB/WB non-diabetic rats, BB/WB showing higher serum concentration and lower cumulative urinary excretion of LC and TC than Wistar animals. Renal clearance of L-carnitine components proved to be markedly higher in BB/BB diabetic rats, as previously shown in streptozotocin rats. The reduction of serum concentration of the carnitines endogenous pool may explain this finding. The lack of an increased urinary excretion of L-carnitine components in diabetic animals despite the high increase of diuresis suggests that the saturable tubular reabsorption of L-carnitine family components also in diabetes is the primary mechanism to preserve the homeostatic equilibria of the L-carnitine family, the variation in serum concentration being attributable to the complex systemic metabolic alterations typical of diabetes. In agreement with previous investigations, male animals of all the strains showed higher serum concentration and urinary excretion of L-carnitine components as compared to females.
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PMID:Serum and urine levels of levocarnitine family components in genetically diabetic rats. 794 43

The rationale for these experiments is that administration of L-carnitine and/or short-chain acylcarnitines attenuates myocardial dysfunction 1) in hearts from diabetic animals (in which L-carnitine levels are decreased); 2) induced by ischemia-reperfusion in hearts from nondiabetic animals; and 3) in nondiabetic humans with ischemic heart disease. The objective of these studies was to investigate whether imbalances in carnitine metabolism play a role in the pathogenesis of diabetic peripheral neuropathy. The major findings in rats with streptozotocin-induced diabetes of 4-6 weeks duration were that 24-h urinary carnitine excretion was increased approximately twofold and L-carnitine levels were decreased in plasma (46%) and sciatic nerve endoneurium (31%). These changes in carnitine levels/excretion were associated with decreased caudal nerve conduction velocity (10-15%) and sciatic nerve changes in Na(+)-K(+)-ATPase activity (decreased 50%), Mg(2+)-ATPase (decreased 65%), 1,2-diacyl-sn-glycerol (DAG) (decreased 40%), vascular albumin permeation (increased 60%), and blood flow (increased 65%). Treatment with acetyl-L-carnitine normalized plasma and endoneurial L-carnitine levels and prevented all of these metabolic and functional changes except the increased blood flow, which was unaffected, and the reduction in DAG, which decreased another 40%. In conclusion, these observations 1) demonstrate a link between imbalances in carnitine metabolism and several metabolic and functional abnormalities associated with diabetic polyneuropathy and 2) indicate that decreased sciatic nerve endoneurial ATPase activity (ouabain-sensitive and insensitive) in this model of diabetes is associated with decreased DAG.
Diabetes 1994 Dec
PMID:Neural dysfunction and metabolic imbalances in diabetic rats. Prevention by acetyl-L-carnitine. 795 1

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

Acetyl-L-carnitine reduces the latencies of electroretinogram oscillatory potentials in healthy humans. The effect of acetyl-L-carnitine (50 mg.kg-1.day-1) on the increased electroretinogram latencies found in rats with STZ-induced hyperglycemia of 3-wk duration was evaluated. The aldose reductase inhibitor sorbinil, which has been shown to normalize abnormal electroretinogram tracings associated with STZ-induced diabetes, was used as a positive control. Aldose reductase inhibitors are thought to lower tissue sorbitol while increasing myo-inositol. The electroretinograms of the STZ-induced diabetic rats in this study were abnormal; treatment with acetyl-L-carnitine as well as sorbinil significantly improved electroretinogram b-wave amplitude and decreased the latencies of oscillatory potentials 2 and 3. Acetyl-L-carnitine treatment of STZ-induced diabetic rats did not affect hyperglycemia or erythrocyte polyol pathway activity as reflected by erythrocyte sorbitol levels. In contrast, sorbinil did reduce elevated erythrocyte sorbitol levels. This suggests that the impaired electroretinograms associated with STZ-induced diabetes may not be caused solely by increased polyol pathway activity.
Diabetes 1993 Aug
PMID:Acetyl-L-carnitine corrects electroretinographic deficits in experimental diabetes. 832 41

Measurement of nerve conduction velocity (NCV) is a useful and sensitive tool for evaluating diabetes related neurological dysfunctions. The method used allows to monitor the parameter at different times in the same group of rats, so that it is possible to observe simultaneously the development of the damage in time, and to evaluate the improvement related to the treatment. The repeated oral treatment with acetyl-L-carnitine (ALC, CAS 5080-50-2) 250 mg/kg caused an improvement in NCV of the diabetic rats; the effect was higher when the treatment started early with respect to the diabetes induction. The improvement in NCV was constant in time and comparable from 2 to 6 weeks of the treatment. In conclusion, oral treatment with ALC was able to normalize the impairment of NCV in streptozotocin rats, the effect being constant in time from 2 to 6 weeks of treatment and up to 8 weeks after induction when administration started in early stage of diabetes (2-3 weeks after induction); however, at this time the NCV is already significantly decreased.
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PMID:Acetyl-L-carnitine effect on nerve conduction velocity in streptozotocin-diabetic rats. 848 65

The effects of propionyl-L-carnitine (PCAL) on caudal motor nerve conduction velocity, the coefficient of variation of the R-R interval on the electrocardiogram, and sciatic nerve blood flow were compared with those of [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate, an aldose reductase inhibitor, in rats with streptozotocin-induced diabetes. Diabetic control rats showed significantly delayed nerve conduction (P < .05), decreased R-R variability (P < .05) and reduced sciatic nerve blood flow (P < .05). Oral administration of PCAL (0.5 g/kg/day) and [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (0.05% in the diet: 60 mg/kg/day) for 8 weeks significantly improved both nerve conduction (P < .05) and R-R variability (P < .05) in diabetic rats, along with the normalization of sciatic nerve blood flow. PCAL treatment increased the nerve tissue levels of carnitine and myo-inositol and reduced the serum triglyceride level in diabetic rats. Our results suggests that PCAL could have therapeutic potential for the treatment of diabetic neuropathy.
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PMID:Effect of propionyl-L-carnitine on motor nerve conduction, autonomic cardiac function, and nerve blood flow in rats with streptozotocin-induced diabetes: comparison with an aldose reductase inhibitor. 855 55

The effect of an analogue of L-carnitine, propionyl-L-carnitine, on the electroretinogram, motor nerve conduction velocity and nerve blood flow was determined in rats with streptozotocin-induced diabetes, and was compared with the effects of insulin alone or combined therapy. Oral administration of propionyl-L-carnitine (3 g/kg daily for 4 weeks) significantly increased caudal nerve motor conduction velocity and sciatic nerve blood flow in diabetic rats. There were no differences in the effects of insulin (8-10 U daily for 4 weeks), propionyl-L-carnitine and combined therapy. Although propionyl-L-carnitine significantly shortened the peak latency of the electroretinogram b-wave in diabetic rats, its effect was far weaker than that of insulin or combined therapy, with combined therapy producing the greatest improvement. These effects of propionyl-L-carnitine were accompanied by a decrease of serum lipid levels, an increase of the sciatic nerve carnitine content, and no changes of the tissue (nerve and retinal) sorbitol and myo-inositol concentrations. In contrast, insulin significantly reduced the tissue sorbitol content and markedly increased myo-inositol. These findings suggest that propionyl-L-carnitine may improve diabetic neuropathy and retinopathy without influencing the polyol pathway, and that this beneficial effect may be mediated through the amelioration of microcirculation and tissue carnitine content, thus probably increasing fatty acid oxidation.
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PMID:Effects of propionyl-L-carnitine and insulin on the electroretinogram, nerve conduction and nerve blood flow in rats with streptozotocin-induced diabetes. 859

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


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