CIDeRplusGeneral Information:
| Id: | 3,388 |
| Diseases: |
Cardiovascular disease
Carnitine deficiency, systemic primary - [OMIM] Diabetes mellitus, type II - [OMIM] Insulin resistance Status epilepticus |
| Mammalia | |
| review | |
| Reference: | Ringseis R et al.(2012) Role of carnitine in the regulation of glucose homeostasis and insulin sensitivity: evidence from in vivo and in vitro studies with carnitine supplementation and carnitine deficiency Eur J Nutr 1: 1-18 [PMID: 22134503] |
Interaction Information:
| Comment | Carnitine is a water soluble quaternary amine (3-hydroxy-4-N,N,N-trimethylaminobutyric acid), which is essential for normal function of all tissues. Dietary sources of carnitine include mainly products of animal origin, such as meat and dairy products. Through an omnivorous diet, approximately 0.3-1.9 mg carnitine is provided per kg body weight and day, whereas vegetarians consume less than 0.02 mg per kg body weight and day. Nonetheless, vegetarians maintain normal carnitine levels indicating that humans also effectively synthesize carnitine, which was estimated to be 0.19 mg carnitine per kg body weight and day. This implies that endogenous synthesis provides 90% of total body carnitine in strict vegetarians and about 25% in omnivores. |
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Formal Description Interaction-ID: 31527 |
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| Comment | In humans, the major sites of carnitine synthesis are the liver and the kidneys because these are the only tissues with a considerable activity of BBD. |
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Formal Description Interaction-ID: 31640 |
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| Drugbank entries | Show/Hide entries for BBOX1 |
| Comment | In humans, the major sites of carnitine synthesis are the liver and the kidneys because these are the only tissues with a considerable activity of BBD. |
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Formal Description Interaction-ID: 31679 |
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| Drugbank entries | Show/Hide entries for BBOX1 |
| Comment | Endogenous carnitine synthesis starts with the release of trimethyllysine (TML) from lysosomal protein breakdown, which is subsequently converted to gamma-butyrobetaine by a series of enzymatic reactions involving trimethyllysine dioxygenase, 3-hydroxy-N-trimethyllysine aldolase, and 4-N-trimethylaminobutyraldehyde dehydrogenase (TMABADH). Finally, gamma-butyrobetaine is hydroxylated by gamma-butyrobetaine dioxygenase (BBD) to form carnitine. |
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Formal Description Interaction-ID: 31680 |
process increases_quantity of drug/chemical compound |
| Comment | In rats, it was demonstrated that carnitine supplementation at levels exceeding the demand decreases carnitine biosynthesis through depressing the activity of BBD. |
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Formal Description Interaction-ID: 31681 |
environment excess carnitine supplementation decreases_activity of process |
| Comment | Since carnitine synthesis is dependent on the availability of several co-factors including the micronutrients vitamin C, vitamin B6, and iron, a deficiency in these nutrients can lead to carnitine deficiency, in particular when carnitine is not provided from the diet in sufficient amounts. |
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Formal Description Interaction-ID: 31682 |
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| Comment | Since carnitine synthesis is dependent on the availability of several co-factors including the micronutrients vitamin C, vitamin B6, and iron, a deficiency in these nutrients can lead to carnitine deficiency, in particular when carnitine is not provided from the diet in sufficient amounts. |
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Formal Description Interaction-ID: 31683 |
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| Comment | Since carnitine synthesis is dependent on the availability of several co-factors including the micronutrients vitamin C, vitamin B6, and iron, a deficiency in these nutrients can lead to carnitine deficiency, in particular when carnitine is not provided from the diet in sufficient amounts. |
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Formal Description Interaction-ID: 31684 |
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| Comment | Delivery of carnitine from plasma into cells is catalyzed by organic cation transporters (OCTNs), from which the OCTN2 isoform is the physiologically most important carnitine transporter. OCTN2 is of great importance for maintaining normal carnitine levels in serum because it is also responsible for tubular reabsorption of carnitine in the kidney where approximately 99% of all free carnitine filtered is reabsorbed when plasma free carnitine concentration is in its normal range. Patients carrying a mutation in the OCTN2 gene develop primary systemic carnitine deficiency with markedly reduced serum carnitine levels because most of the filtered carnitine is lost in the urine. |
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Formal Description Interaction-ID: 31685 |
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| Drugbank entries | Show/Hide entries for SLC22A5 |
| Comment | Delivery of carnitine from plasma into cells is catalyzed by organic cation transporters (OCTNs), from which the OCTN2 isoform is the physiologically most important carnitine transporter. OCTN2 is of great importance for maintaining normal carnitine levels in serum because it is also responsible for tubular reabsorption of carnitine in the kidney where approximately 99% of all free carnitine filtered is reabsorbed when plasma free carnitine concentration is in its normal range. Patients carrying a mutation in the OCTN2 gene develop primary systemic carnitine deficiency with markedly reduced serum carnitine levels because most of the filtered carnitine is lost in the urine. |
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Formal Description Interaction-ID: 31688 |
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| Drugbank entries | Show/Hide entries for SLC22A5 |
| Comment | Delivery of carnitine from plasma into cells is catalyzed by organic cation transporters (OCTNs), from which the OCTN2 isoform is the physiologically most important carnitine transporter. OCTN2 is of great importance for maintaining normal carnitine levels in serum because it is also responsible for tubular reabsorption of carnitine in the kidney where approximately 99% of all free carnitine filtered is reabsorbed when plasma free carnitine concentration is in its normal range. Patients carrying a mutation in the OCTN2 gene develop primary systemic carnitine deficiency with markedly reduced serum carnitine levels because most of the filtered carnitine is lost in the urine. |
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Formal Description Interaction-ID: 31690 |
gene/protein mutant increases_activity of |
| Comment | Carnitine functions in the intermediary metabolism via its role in fatty acid catabolism by facilitating the translocation of long-chain fatty acids (acyl groups) from the cytosol into the mitochondrial matrix for subsequent beta-oxidation. This complicated translocation process is catalyzed by the action of three carnitine-dependent enzymes that together represent the carnitine shuttle system. |
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Formal Description Interaction-ID: 31691 |
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| Comment | Carnitine functions in the intermediary metabolism via its role in fatty acid catabolism by facilitating the translocation of long-chain fatty acids (acyl groups) from the cytosol into the mitochondrial matrix for subsequent beta-oxidation. This complicated translocation process is catalyzed by the action of three carnitine-dependent enzymes that together represent the carnitine shuttle system. |
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Formal Description Interaction-ID: 31693 |
drug/chemical compound affects_activity of process |
| Comment | Carnitine functions in the intermediary metabolism via its role in fatty acid catabolism by facilitating the translocation of long-chain fatty acids (acyl groups) from the cytosol into the mitochondrial matrix for subsequent beta-oxidation. This complicated translocation process is catalyzed by the action of three carnitine-dependent enzymes that together represent the carnitine shuttle system. |
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Formal Description Interaction-ID: 31695 |
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| Comment | Carnitine functions in the intermediary metabolism via its role in fatty acid catabolism by facilitating the translocation of long-chain fatty acids (acyl groups) from the cytosol into the mitochondrial matrix for subsequent beta-oxidation. This complicated translocation process is catalyzed by the action of three carnitine-dependent enzymes that together represent the carnitine shuttle system. |
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Formal Description Interaction-ID: 31696 |
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| Comment | Since intracellular accumulation of acyl-CoA derivatives has been implicated in the development of insulin resistance in skeletal muscle and heart, carnitine supplementation has gained attention as a tool for the treatment or prevention of insulin resistance and type 2 diabetes mellitus. Other studies point toward a causative role for carnitine deficiency in developing mitochondrial dysfunction and insulin resistance during states of chronic metabolic stress such as obesity and aging, which can be reversed by oral carnitine supplementation. |
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Formal Description Interaction-ID: 31801 |
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| Comment | Since intracellular accumulation of acyl-CoA derivatives has been implicated in the development of insulin resistance in skeletal muscle and heart, carnitine supplementation has gained attention as a tool for the treatment or prevention of insulin resistance and type 2 diabetes mellitus. Other studies point toward a causative role for carnitine deficiency in developing mitochondrial dysfunction and insulin resistance during states of chronic metabolic stress such as obesity and aging, which can be reversed by oral carnitine supplementation. |
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Formal Description Interaction-ID: 31802 |
phenotype carnitine deficiency increases_activity of disease Insulin resistance |
| Comment | Since intracellular accumulation of acyl-CoA derivatives has been implicated in the development of insulin resistance in skeletal muscle and heart, carnitine supplementation has gained attention as a tool for the treatment or prevention of insulin resistance and type 2 diabetes mellitus. Other studies point toward a causative role for carnitine deficiency in developing mitochondrial dysfunction and insulin resistance during states of chronic metabolic stress such as obesity and aging, which can be reversed by oral carnitine supplementation. |
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Formal Description Interaction-ID: 31803 |
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| Comment | The majority of the studies (11 out of 16) revealed an improvement of parameters of glucose tolerance, like fasting plasma glucose, fasting plasma insulin, area under the curve for glucose, area under the curve for insulin, glucose oxidation rate and/or homeostasis model assessment of insulin resistance (HOMA-IR), by carnitine supplementation. The improvement of glucose tolerance following carnitine supplementation in these studies was independent of the route of carnitine administration (i.v. vs. oral), the treatment duration, the metabolic disorder of the subjects [pre-diabetic, diabetic, overweight/obese, or patients with nonalcoholic steatohepatitis (NASH), chronic renal failure, or home parenteral nutrition (HPN)], the carnitine formulation [carnitine vs. acetyl-L-carnitine (ALC) or carnitinetartrate], or the carnitine dosage. However, it has to be considered that in two of the studies with a positive outcome, carnitine supplementation (2 g oral carnitine) was studied in combination with an anti-obesity drug (either orlistat or sibutramin) compared to monotherapy with the anti-obesity drugs. |
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Formal Description Interaction-ID: 31804 |
environment carnitine supplementation decreases_activity of disease Insulin resistance |
| Comment | Only six human studies with healthy subjects reporting an effect of carnitine supplementation on parameters of glucose tolerance and insulin sensitivity were identified. Five of these studies showed an improvement of parameters of glucose tolerance in response to carnitine supplementation, whereas the remaining study did not reveal an improved glucose tolerance as evidenced by unaltered fasting glucose and fasting insulin levels. |
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Formal Description Interaction-ID: 31805 |
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| Comment | In one of the studies with a positive outcome, the effect of 3 g oral carnitine-tartrate supplementation was directly compared in both healthy (normal weight) and overweight/obese subjects to elucidate whether the response of glucose tolerance is different between these two groups. This study indeed revealed that carnitine-tartrate reduced the area under the curve for glucose AUC(GLC) following an oral glucose tolerance test only in the normal-weight subjects, but not in the overweight/obese subjects indicating that carnitine supplementation is not useful in subjects with metabolic disorders. Considering the great number of studies reporting beneficial effects of carnitine supplementation in obese or diabetic subjects, it cannot be deduced from one study that the effect of carnitine on glucose tolerance is dependent on the health/metabolic status. |
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Formal Description Interaction-ID: 31806 |
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| Comment | In one of the studies with a positive outcome, the effect of 3 g oral carnitine-tartrate supplementation was directly compared in both healthy (normal weight) and overweight/obese subjects to elucidate whether the response of glucose tolerance is different between these two groups. This study indeed revealed that carnitine-tartrate reduced the area under the curve for glucose AUC(GLC) following an oral glucose tolerance test only in the normal-weight subjects, but not in the overweight/obese subjects indicating that carnitine supplementation is not useful in subjects with metabolic disorders. Considering the great number of studies reporting beneficial effects of carnitine supplementation in obese or diabetic subjects, it cannot be deduced from one study that the effect of carnitine on glucose tolerance is dependent on the health/metabolic status. |
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Formal Description Interaction-ID: 31807 |
disease Metabolic disorder affects_activity of environment carnitine supplementation |
| Comment | A total of ten studies were considered as suitable to evaluate the relationship between carnitine deficiency and glucose tolerance in humans and animals. Only four of these studies revealed that carnitine deficiency is associated with an impaired glucose tolerance, whereas the remaining six studies could not establish this association. |
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Formal Description Interaction-ID: 31808 |
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| Comment | In humans, secondary carnitine deficiency is observed during treatment with valproic acid, a broad-spectrum anti-epileptic drug that is now used commonly for several other neurological and psychiatric indications. |
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Formal Description Interaction-ID: 31809 |
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| Drugbank entries | Show/Hide entries for Valproic acid |
| Comment | In humans, secondary carnitine deficiency is observed during treatment with valproic acid, a broad-spectrum anti-epileptic drug that is now used commonly for several other neurological and psychiatric indications. |
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Formal Description Interaction-ID: 31813 |
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| Drugbank entries | Show/Hide entries for Valproic acid |
| Comment | Valproic acid contributes to carnitine deficiency through decreasing the concentration of alpha-ketoglutarate that is required for de novo biosynthesis of carnitine. |
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Formal Description Interaction-ID: 31814 |
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| Drugbank entries | Show/Hide entries for Valproic acid |
| Comment | Valproic acid contributes to carnitine deficiency through decreasing the concentration of alpha-ketoglutarate that is required for de novo biosynthesis of carnitine. |
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Formal Description Interaction-ID: 31815 |
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| Comment | Evidence exist that serious complications occurring in some patients receiving valproic acid chronically, such as hepatotoxicity and hyperammonemic encephalopathy, are promoted by carnitine deficiency, wherefore carnitine supplementation during valproic acid therapy in high risk patients, such as children, is generally recommended. |
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Formal Description Interaction-ID: 31816 |
phenotype secondary carnitine deficiency increases_activity of phenotype |
| Comment | Evidence exist that serious complications occurring in some patients receiving valproic acid chronically, such as hepatotoxicity and hyperammonemic encephalopathy, are promoted by carnitine deficiency, wherefore carnitine supplementation during valproic acid therapy in high risk patients, such as children, is generally recommended. |
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Formal Description Interaction-ID: 31817 |
phenotype secondary carnitine deficiency increases_activity of phenotype hyperammonemic encephalopathy |
| Comment | In one study in 23 psychiatric patients with chronic valproic acid treatment and documented hypocarnitinemia, increased fasting plasma glucose levels were reported indicating that an impaired carnitine status contributes to glucose intolerance in humans. |
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Formal Description Interaction-ID: 31818 |
phenotype secondary carnitine deficiency increases_activity of phenotype |
| Comment | Pivalate administration causes induction of secondary carnitine deficiency due to excessive loss of carnitine via the urine through formation of pivaloylcarnitine. In studies using the pivalate model of carnitine deficiency, glucose tolerance was not significantly impaired by pivalate treatment. |
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Formal Description Interaction-ID: 31819 |
drug/chemical compound Pivalic acid increases_activity of phenotype secondary carnitine deficiency |
| Comment | Pivalate administration causes induction of secondary carnitine deficiency due to excessive loss of carnitine via the urine through formation of pivaloylcarnitine. In studies using the pivalate model of carnitine deficiency, glucose tolerance was not significantly impaired by pivalate treatment. |
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Formal Description Interaction-ID: 31820 |
phenotype secondary carnitine deficiency NOT affects_activity of phenotype |
| Comment | High-fat diet induces carnitine deficiency. Long-term feeding of a high-fat diet impairs whole body carnitine status due to compromising the capacity of the liver to synthesize and take up carnitine.As the underlying mechanism of high-fat diet administration, reduction of transcript levels of genes responsible for carnitine synthesis, such as BBD and TMABA-DH, and carnitine uptake (OCTNs) has been identified. |
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Formal Description Interaction-ID: 31821 |
environment high-fat diet increases_activity of phenotype carnitine deficiency |
| Comment | It has been postulated that the reduced transcript levels of the respective genes is due to disruption of peroxisome proliferator-activated receptor alpha (PPARalpha) function in response to high-fat diet administration, because PPARalpha has been identified as a critical transcriptional regulator of BBD, TMABA-DH, and OCTN2 in mice, rats, and pigs. |
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Formal Description Interaction-ID: 31822 |
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| Drugbank entries | Show/Hide entries for PPARA or BBOX1 |
| Comment | It has been postulated that the reduced transcript levels of the respective genes is due to disruption of peroxisome proliferator-activated receptor alpha (PPARalpha) function in response to high-fat diet administration, because PPARalpha has been identified as a critical transcriptional regulator of BBD, TMABA-DH, and OCTN2 in mice, rats, and pigs. |
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Formal Description Interaction-ID: 31823 |
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| Drugbank entries | Show/Hide entries for PPARA or ALDH9A1 |
| Comment | It has been postulated that the reduced transcript levels of the respective genes is due to disruption of peroxisome proliferator-activated receptor alpha (PPARalpha) function in response to high-fat diet administration, because PPARalpha has been identified as a critical transcriptional regulator of BBD, TMABA-DH, and OCTN2 in mice, rats, and pigs. |
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Formal Description Interaction-ID: 31824 |
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| Drugbank entries | Show/Hide entries for PPARA or SLC22A5 |
| Comment | Regular endurance exercise caused a significant increase in the hepatic expression of BBD, TMABA-DH, and OCTN2 in mice fed the high-fat diet indicating that endurance exercise is capable of completely reversing the high-fat diet-induced impairment of hepatic carnitine status by stimulating carnitine synthesis and uptake. |
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Formal Description Interaction-ID: 31825 |
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| Drugbank entries | Show/Hide entries for BBOX1 |
| Comment | Regular endurance exercise caused a significant increase in the hepatic expression of BBD, TMABA-DH, and OCTN2 in mice fed the high-fat diet indicating that endurance exercise is capable of completely reversing the high-fat diet-induced impairment of hepatic carnitine status by stimulating carnitine synthesis and uptake. |
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Formal Description Interaction-ID: 31826 |
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| Drugbank entries | Show/Hide entries for ALDH9A1 |
| Comment | Regular endurance exercise caused a significant increase in the hepatic expression of BBD, TMABA-DH, and OCTN2 in mice fed the high-fat diet indicating that endurance exercise is capable of completely reversing the high-fat diet-induced impairment of hepatic carnitine status by stimulating carnitine synthesis and uptake. |
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Formal Description Interaction-ID: 31827 |
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| Drugbank entries | Show/Hide entries for SLC22A5 |
| Comment | Regular endurance exercise caused a significant increase in the hepatic expression of BBD, TMABA-DH, and OCTN2 in mice fed the high-fat diet indicating that endurance exercise is capable of completely reversing the high-fat diet-induced impairment of hepatic carnitine status by stimulating carnitine synthesis and uptake. |
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Formal Description Interaction-ID: 31828 |
environment exercise increases_activity of process |
| Comment | Regular endurance exercise caused a significant increase in the hepatic expression of BBD, TMABA-DH, and OCTN2 in mice fed the high-fat diet indicating that endurance exercise is capable of completely reversing the high-fat diet-induced impairment of hepatic carnitine status by stimulating carnitine synthesis and uptake. |
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Formal Description Interaction-ID: 31829 |
environment exercise increases_activity of process renal carnitine reabsorption |
| Comment | Another approach to induce carnitine deficiency is administration of the pharmacological agent mildronate, which reduces carnitine levels in plasma and heart via inhibiting BBD and OCTN2. Mildronate is a cardioprotective drug whose mechanism of action is based on reducing the availability of carnitine. |
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Formal Description Interaction-ID: 31830 |
drug/chemical compound Mildronate increases_activity of phenotype carnitine deficiency |
| Comment | Another approach to induce carnitine deficiency is administration of the pharmacological agent mildronate, which reduces carnitine levels in plasma and heart via inhibiting BBD and OCTN2. Mildronate is a cardioprotective drug whose mechanism of action is based on reducing the availability of carnitine. |
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Formal Description Interaction-ID: 31831 |
drug/chemical compound Mildronate decreases_activity of disease Cardiovascular disease |
| Comment | Another approach to induce carnitine deficiency is administration of the pharmacological agent mildronate, which reduces carnitine levels in plasma and heart via inhibiting BBD and OCTN2. Mildronate is a cardioprotective drug whose mechanism of action is based on reducing the availability of carnitine. |
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Formal Description Interaction-ID: 31832 |
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| Drugbank entries | Show/Hide entries for BBOX1 |
| Comment | Another approach to induce carnitine deficiency is administration of the pharmacological agent mildronate, which reduces carnitine levels in plasma and heart via inhibiting BBD and OCTN2. Mildronate is a cardioprotective drug whose mechanism of action is based on reducing the availability of carnitine. |
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Formal Description Interaction-ID: 31833 |
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| Drugbank entries | Show/Hide entries for SLC22A5 |
| Comment | Carnitine deficiency induced by mildronate improves glucose tolerance whereas carnitine deficiency in JVS mice is accompanied by an impaired glucose tolerance. Results from animal studies investigating the possible association between carnitine deficiency and glucose intolerance are conflicting. Only four studies revealed a direct relationship between carnitine deficiency and glucose intolerance, whereas the majority of studies dealing with this question could not establish this relationship. Further studies are necessary to explain the apparently conflicting observation that both carnitine deficiency induced by mildronate and pharmacological supplementation with carnitine can stimulate glucose metabolism. |
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Formal Description Interaction-ID: 31834 |
phenotype carnitine deficiency decreases_activity of phenotype |
| Comment | Six of eight studies reported that diabetic subjects have reduced plasma free carnitine concentrations. |
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Formal Description Interaction-ID: 31836 |
disease increases_activity of phenotype |
| Comment | One important mechanism by which carnitine improves insulin sensitivity represents enhancement of mitochondrial oxidation of long-chain acyl-CoAs. Accumulation of long-chain acyl-CoAs and other fatty acid metabolites impair insulin signaling and therefore contribute to the development of insulin resistance in skeletal muscle and heart. |
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Formal Description Interaction-ID: 31837 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Comment | One important mechanism by which carnitine improves insulin sensitivity represents enhancement of mitochondrial oxidation of long-chain acyl-CoAs. Accumulation of long-chain acyl-CoAs and other fatty acid metabolites impair insulin signaling and therefore contribute to the development of insulin resistance in skeletal muscle and heart. |
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Formal Description Interaction-ID: 31838 |
drug/chemical compound decreases_activity of |
| Comment | A large body of evidence suggests that carnitine and its derivatives acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) enhance glucose utilization by stimulating the activity of the pyruvate dehydrogenase complex (PDHC), which is a key enzymatic complex in glucose oxidation, because intramitochondrial acetyl-CoA can be converted with carnitine into ALC via the carnitine acetyltransferase that is then transported out of the mitochondria. Therefore, carnitine strongly reduces intramitochondrial acetyl-CoA levels resulting in a 10- to 20-fold decrease in the acetyl-CoA/CoA ratio. |
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Formal Description Interaction-ID: 31839 |
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| Comment | A large body of evidence suggests that carnitine and its derivatives acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) enhance glucose utilization by stimulating the activity of the pyruvate dehydrogenase complex (PDHC), which is a key enzymatic complex in glucose oxidation, because intramitochondrial acetyl-CoA can be converted with carnitine into ALC via the carnitine acetyltransferase that is then transported out of the mitochondria. Therefore, carnitine strongly reduces intramitochondrial acetyl-CoA levels resulting in a 10- to 20-fold decrease in the acetyl-CoA/CoA ratio. |
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Formal Description Interaction-ID: 31840 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Comment | Modulation of pyruvate dehydrogenase complex (PDHC) activity is probably an important mechanism through which carnitine exerts an effect on whole body glucose homeostasis. However, whether carnitine has a stimulatory or inhibitory effect on PDHC activity is probably dependent on several factors including the metabolic and health status (e.g. normo-insulinemic vs. hyperinsulinemic) of the subjects. |
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Formal Description Interaction-ID: 31841 |
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| Comment | In the JVS mouse model of primary carnitine deficiency hepatic transcript levels of glycolytic enzymes such as glucokinase and pyruvate kinase are reduced, whereas hepatic transcript level of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK1) is increased in this genetic model of carnitine deficiency. |
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Formal Description Interaction-ID: 31843 |
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| Drugbank entries | Show/Hide entries for GCK |
| Comment | In the JVS mouse model of primary carnitine deficiency hepatic transcript levels of glycolytic enzymes such as glucokinase and pyruvate kinase are reduced, whereas hepatic transcript level of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK1) is increased in this genetic model of carnitine deficiency. |
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Formal Description Interaction-ID: 31848 |
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| Drugbank entries | Show/Hide entries for PKLR |
| Comment | In the JVS mouse model of primary carnitine deficiency hepatic transcript levels of glycolytic enzymes such as glucokinase and pyruvate kinase are reduced, whereas hepatic transcript level of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK1) is increased in this genetic model of carnitine deficiency. |
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Formal Description Interaction-ID: 31849 |
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| Comment | In the JVS mouse model of primary carnitine deficiency hepatic transcript levels of glycolytic enzymes such as glucokinase and pyruvate kinase are reduced, whereas hepatic transcript level of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK1) is increased in this genetic model of carnitine deficiency. |
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Formal Description Interaction-ID: 31850 |
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| Comment | In the JVS mouse model of primary carnitine deficiency hepatic transcript levels of glycolytic enzymes such as glucokinase and pyruvate kinase are reduced, whereas hepatic transcript level of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK1) is increased in this genetic model of carnitine deficiency. |
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Formal Description Interaction-ID: 31852 |
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| Drugbank entries | Show/Hide entries for PCK1 |
| Comment | Carnitine supplementation increased expression of genes involved in glucose transport (e.g., GLUT8), conversion of glucose into glucose 6-phosphate (hexokinase D), and glycolysis (e.g., glycerol-3-phosphate dehydrogenase) and leads to increased glucose oxidation in the liver of pigs. Genes involved in gluconeogenesis (e.g., PCK1, FBP2) were down-regulated in pig liver by carnitine supplementation. |
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Formal Description Interaction-ID: 31853 |
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| Comment | Carnitine supplementation increased expression of genes involved in glucose transport (e.g., GLUT8), conversion of glucose into glucose 6-phosphate (hexokinase D), and glycolysis (e.g., glycerol-3-phosphate dehydrogenase) and leads to increased glucose oxidation in the liver of pigs. Genes involved in gluconeogenesis (e.g., PCK1, FBP2) were down-regulated in pig liver by carnitine supplementation. |
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Formal Description Interaction-ID: 31854 |
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| Drugbank entries | Show/Hide entries for GCK |
| Comment | Carnitine supplementation increased expression of genes involved in glucose transport (e.g., GLUT8), conversion of glucose into glucose 6-phosphate (hexokinase D), and glycolysis (e.g., glycerol-3-phosphate dehydrogenase) and leads to increased glucose oxidation in the liver of pigs. Genes involved in gluconeogenesis (e.g., PCK1, FBP2) were down-regulated in pig liver by carnitine supplementation. |
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Formal Description Interaction-ID: 31855 |
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| Drugbank entries | Show/Hide entries for GPD1 |
| Comment | Carnitine supplementation increased expression of genes involved in glucose transport (e.g., GLUT8), conversion of glucose into glucose 6-phosphate (hexokinase D), and glycolysis (e.g., glycerol-3-phosphate dehydrogenase) and leads to increased glucose oxidation in the liver of pigs. Genes involved in gluconeogenesis (e.g., PCK1, FBP2) were down-regulated in pig liver by carnitine supplementation. |
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Formal Description Interaction-ID: 31856 |
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| Drugbank entries | Show/Hide entries for PCK1 |
| Comment | Carnitine supplementation increased expression of genes involved in glucose transport (e.g., GLUT8), conversion of glucose into glucose 6-phosphate (hexokinase D), and glycolysis (e.g., glycerol-3-phosphate dehydrogenase) and leads to increased glucose oxidation in the liver of pigs. Genes involved in gluconeogenesis (e.g., PCK1, FBP2) were down-regulated in pig liver by carnitine supplementation. |
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Formal Description Interaction-ID: 31857 |
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| Comment | Carnitine supplementation alters the expression of genes involved in the insulin signaling cascade, like insulin receptor substrate-2, phosphatidylinositol 3-kinase regulatory alpha subunit, and receptor protein-tyrosine kinase erbB-3 precursor. |
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Formal Description Interaction-ID: 31858 |
environment carnitine supplementation affects_activity of |
| Comment | Carnitine supplementation alters the expression of genes involved in the insulin signaling cascade, like insulin receptor substrate-2, phosphatidylinositol 3-kinase regulatory alpha subunit, and receptor protein-tyrosine kinase erbB-3 precursor. |
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Formal Description Interaction-ID: 31859 |
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| Comment | Carnitine supplementation alters the expression of genes involved in the insulin signaling cascade, like insulin receptor substrate-2, phosphatidylinositol 3-kinase regulatory alpha subunit, and receptor protein-tyrosine kinase erbB-3 precursor. |
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Formal Description Interaction-ID: 31860 |
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| Drugbank entries | Show/Hide entries for PIK3R1 |
| Comment | Carnitine supplementation alters the expression of genes involved in the insulin signaling cascade, like insulin receptor substrate-2, phosphatidylinositol 3-kinase regulatory alpha subunit, and receptor protein-tyrosine kinase erbB-3 precursor. |
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Formal Description Interaction-ID: 31861 |
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| Comment | In streptozotocin-induced diabetic rats, liver IGF-1 mRNA expression is reduced but is restored by carnitine supplementation. |
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Formal Description Interaction-ID: 31862 |
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| Drugbank entries | Show/Hide entries for IGF1 |
| Comment | Carnitine supplementation alters expression of genes dealing with IGF binding, such as IGF-1 receptor, and 3-phosphoinositide-dependent protein kinase-1. |
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Formal Description Interaction-ID: 31863 |
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| Drugbank entries | Show/Hide entries for IGF1R |
| Comment | Carnitine supplementation alters expression of genes dealing with IGF binding, such as IGF-1 receptor, and 3-phosphoinositide-dependent protein kinase-1. |
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Formal Description Interaction-ID: 31864 |
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| Drugbank entries | Show/Hide entries for PDPK1 |
| Comment | Studies in animals and humans revealed that carnitine influences the IGF axis by increasing plasma concentrations of IGF-1 and IGF-2. |
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Formal Description Interaction-ID: 31865 |
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| Drugbank entries | Show/Hide entries for IGF1 |
| Comment | Studies in animals and humans revealed that carnitine influences the IGF axis by increasing plasma concentrations of IGF-1 and IGF-2. |
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Formal Description Interaction-ID: 31866 |
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| Comment | Carnitine activates the IGF-1 signaling pathway and the latter is possibly linked to the improvement of glucose tolerance. |
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Formal Description Interaction-ID: 31867 |
drug/chemical compound increases_activity of |