Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Summary In this study we investigated the effect of the acetyl-L-carnitine (ALC) supplementation on the myenteric neurons of the jejunum of rats made diabetic at the age of 105 days by streptozotocin (35 mg/kg body weight). Four groups were used: non-diabetic (C), non-diabetic supplemented with ALC (CC), diabetic (D), diabetic supplemented with ALC (DC). After 15 weeks of diabetes induction the blood was collected by cardiac puncture to evaluate glycaemia and glycated haemoglobin. Next the animals were killed and the jejunum was collected and subjected to whole-mount preparation to evidence the myenteric neurons through the histochemical technique of the NADH-diaphorase. The neuronal counts were made in 80 microscopic fields, in tissue samples of five animals of each group. The profiles of the cell bodies of 1000 neurons per group were analysed. Diabetes induced a significant increase in the area of the cell body and decrease in the number of NADH-diaphorase positive myoenteric neurons. ALC suplementation to the diabetic group promoted smaller hypertrophic effects and less neuronal loss than in the myoenteric neurons of the diabetic rats, and in addition diminished the body weight decrease and reduced the fasting glycaemia.
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PMID:Morphometric and quantitative evaluation of the NADH-diaphorase positive myenteric neurons of the jejunum of streptozotocin-diabetic rats supplemented with acetyl-L-carnitine. 1592 29

Hypoglycemia sometimes occurs in patients with diabetes mellitus who receive excessive doses of insulin. Severe hypoglycemia has been known to induce mitochondrial swelling followed by neuronal death in the brain. Since L-carnitine effectively preserves mitochondrial function in various cells both in vitro and in vivo, we investigated its effects on the neuronal damage induced by hypoglycemic insult in male Wistar rats. Animals were given L-carnitine-containing water (0.1%) for 1 week and then received insulin (20 U/kg, i.p.) to induce hypoglycemia. Although L-carnitine did not affect the mortality of animals that developed hypoglycemic shock, it improved the cognitive function of the survived animals as assessed by the Morris water-maze test. L-carnitine effectively inhibited the increase in oxidized glutathione and mitochondrial dysfunction in the hippocampus and prevented neuronal injury. L-carnitine also inhibited the decrease in mitochondrial membrane potential and the generation of reactive oxygen species in hippocampal neuronal cells cultured in glucose-deprived medium. These results suggest that L-carnitine prevents hypoglycemia-induced neuronal damage in the hippocampus, presumably by preserving mitochondrial functions. Thus, L-carnitine may have therapeutic potential in patients with hypoglycemia induced by insulin overdose.
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PMID:L-carnitine inhibits hypoglycemia-induced brain damage in the rat. 1605 Dec 3

A 45-year-old male patient had an episode of acute renal failure with myoglobinuria, myalgias, weakness, and markedly increased serum CK levels. Similar episodes had occurred in the past. Carnitine palmitoyl-transferase II (CPT II) deficiency was documented both biochemically and genetically. Interestingly, muscle biopsy also showed some ragged red fibers (RRF) and complete mitochondrial DNA (mtDNA) sequence disclosed a homoplasmic T3394C point mutation. This mutation is described in Leber's hereditary optic neuropathy (LHON) or in patients with diabetes mellitus.
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PMID:A case of CPT deficiency, homoplasmic mtDNA mutation and ragged red fibers at muscle biopsy. 1616 41

In this work, we investigated the effect of the acetyl-L-carnitine (ALC) supplementation (200 mg/kg/day) on the myenteric neurons of the ileum of rats made diabetic by streptozotocin (35 mg/kg, i.v.). Four groups were used: diabetic (D), diabetic supplemented with ALC (DC), control (C) and control supplemented with ALC (CC). After 15 weeks of diabetes induction the animals were killed and the ileum was collected and subjected to whole-mount preparation to evidence the myenteric neurons through the histochemical technique of the NADH-diaphorase. The density of neurons seen in 12.72 mm2 of ileum showed no difference among the groups, although in group D it was 22% smaller than in group C, while group DC was 9% smaller to group CC. The profiles of the cell bodies (PC) of 1000 neurons per group were analysed. The neurons PC in group D decreased (P < 0.0001) when compared with other groups and increased (P < 0.0001) when compared with group DC. The incidence of neurons with a PC inferior to 200 microm2 was larger in group D. The frequency of neurons with a PC higher than 200 microm2 in group DC was close to those seen in groups C and CC. We concluded that ALC eases the loss of neurons and makes the incidence of myenteric neurons with a PC higher than 200 microm2 similar to the control rats.
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PMID:Morphoquantitative aspects of NADH-diaphorase myenteric neurons in the ileum of diabetic rats treated with acetyl-L-carnitine. 1643 67

Carnitine palmitoyltransferases 1 and 2 (CPTs) facilitate the import of long-chain fatty acids into mitochondria. Modulation of the catalytic activity of the CPT system is currently under investigation for the development of novel drugs against diabetes mellitus. We report here the 1.6 A resolution structure of the full-length mitochondrial membrane protein CPT-2. The structure of CPT-2 in complex with the generic CPT inhibitor ST1326 ([R]-N-[tetradecylcarbamoyl]-aminocarnitine), a substrate analog mimicking palmitoylcarnitine and currently in clinical trials for diabetes mellitus treatment, was solved at 2.5 A resolution. These structures of CPT-2 provide insight into the function of residues involved in substrate binding and determination of substrate specificity, thereby facilitating the rational design of antidiabetic drugs. We identify a sequence insertion found in CPT-2 that mediates membrane localization. Mapping of mutations described for CPT-2 deficiency, a hereditary disorder of lipid metabolism, implies effects on substrate recognition and structural integrity of CPT-2.
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PMID:The crystal structure of carnitine palmitoyltransferase 2 and implications for diabetes treatment. 1661 1

Carnitine acyltransferases catalyze the reversible exchange of acyl groups between coenzyme A (CoA) and carnitine. They have important roles in many cellular processes, especially the oxidation of long-chain fatty acids in the mitochondria for energy production, and are attractive targets for drug discovery against diabetes and obesity. To help define in molecular detail the catalytic mechanism of these enzymes, we report here the high resolution crystal structure of wild-type murine carnitine acetyltransferase (CrAT) in a ternary complex with its substrates acetyl-CoA and carnitine, and the structure of the S554A/M564G double mutant in a ternary complex with the substrates CoA and hexanoylcarnitine. Detailed analyses suggest that these structures may be good mimics for the Michaelis complexes for the forward and reverse reactions of the enzyme, representing the first time that such complexes of CrAT have been studied in molecular detail. The structural information provides significant new insights into the catalytic mechanism of CrAT and possibly carnitine acyltransferases in general.
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PMID:Crystal structures of murine carnitine acetyltransferase in ternary complexes with its substrates. 1687 Jun 16

Peripheral neuropathy (PN), associated with diabetes, neurotoxic chemotherapy, human immunodeficiency virus (HIV)/antiretroviral drugs, alcoholism, nutrient deficiencies, heavy metal toxicity, and other etiologies, results in significant morbidity. Conventional pain medications primarily mask symptoms and have significant side effects and addiction profiles. However, a widening body of research indicates alternative medicine may offer significant benefit to this patient population. Alpha-lipoic acid, acetyl-L-carnitine, benfotiamine, methylcobalamin, and topical capsaicin are among the most well-researched alternative options for the treatment of PN. Other potential nutrient or botanical therapies include vitamin E, glutathione, folate, pyridoxine, biotin, myo-inositol, omega-3 and -6 fatty acids, L-arginine, L-glutamine, taurine, N-acetylcysteine, zinc, magnesium, chromium, and St. John's wort. In the realm of physical medicine, acupuncture, magnetic therapy, and yoga have been found to provide benefit. New cutting-edge conventional therapies, including dual-action peptides, may also hold promise.
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PMID:Peripheral neuropathy: pathogenic mechanisms and alternative therapies. 1717 68

The purpose of the study was to investigate the effects of L-carnitine (CA) on the susceptibility of erythrocyte (RBC) to peroxide-induced lipid oxidation, RBC membrane composition, ATPases activity and oxidative stress in fructose-fed hyperinsulinemic rats. The rats were subjected to experimental hyperinsulinemia and hyperglycemia by feeding a high fructose diet (60 g/100 g) for 6 weeks. The rats showed significant alterations in the RBC membrane composition. The protein content was lower than control animals, while cholesterol, phospholipids and free fatty acids were higher in fructose-fed animals. Significant differences in the total carbohydrate and relative proportions of hexose, hexosamine, sialic acid and fucose of membranes were observed. In these rats, membrane-bound ATPases (total ATPase, Na+, K+ ATPase, Mg2+ and Ca2+ ATPases) were significantly lower while thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LHP) in RBC membrane were significantly higher than those of control rats. The red cells were more susceptible to peroxide-induced oxidative stress that correlated with reduced levels of vitamin E found RBC membrane. When fructose-diet fed rats were treated simultaneously with CA (300 mg/kg b.w/day, i.p.), such alterations in membrane composition and enzyme activities did not occur. Effects of fructose loading on lipid peroxidation was also alleviated by CA. These findings suggest that high levels of dietary fructose is detrimental to RBC membrane integrity and that CA may have membrane stabilizing effects in this diet-induced model of type 2-diabetes.
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PMID:Effects of L-carnitine on RBC membrane composition and function in hyperinsulinemic rats. 1751 55

Glycation-initiated changes in tissue proteins are suggested to play an important role in the development of diabetes-related pathological changes. The purpose of this study was to examine the anti-glycating effect of L-carnitine (CA) in vivo in the high-fructose diet-fed rat and to determine the potential of CA to inhibit in vitro glycation. Additionally the glucose-disposal efficiency of CA in the rat diaphragm was investigated. High-fructose diet (60 g/100 g diet)-fed rats were treated with CA (300 mg/kg/day i.p.) for 60 days. The effect of CA on glucose, fructose and fructosamine in plasma, methyl glyoxal and glycated haemoglobin in whole blood and skin and tail tendon collagen glycation were determined. The inhibitory effect of CA on the glycation of bovine serum albumin in vitro was compared with that of aminoguanidine (AG), a known antiglycation agent. Glucose utilisation induced by insulin in the control rat diaphragm was monitored in the presence and absence of CA. High-fructose feeding induced hyperglycaemia and glycation of haemoglobin and skin and tail tendon collagen. In CA-administered fructose-fed rats glycation was significantly reduced. In vitro glycation and accumulation of advanced glycation end products were mitigated by CA. CA was more effective than AG in inhibiting glycation in vitro. CA also enhanced the utilisation of glucose in the rat diaphragm. The findings of the study reveal that CA not only has antiglycation effect but also enhances glucose disposal in the rat diaphragm. These findings provide evidence for the therapeutic utility of CA in diabetes and associated complications.
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PMID:L-Carnitine inhibits protein glycation in vitro and in vivo: evidence for a role in diabetic management. 1753 Apr 72

Modulation of myocardial free fatty acid metabolism is the key target for metabolic interventions in patients with coronary artery disease (CAD) with diabetes mellitus (DM). Because of its beneficial effects on heart metabolism at rest and on myocardial ischemia and left ventricular function, trimetazidine should be always combined with classical anti-ischemic treatment in patients with DM with CAD. We believe that, the new metabolic agents including L-carnitine, dichloroacetate, perhexiline and etomoxir will be added into our arsenal for the battle against CAD especially in patients with DM in the near future.
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PMID:Metabolic agents in the management of diabetic coronary patients: a new era. 1819 1


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