CIDeRplusGeneral Information:
| Id: | 2,306 |
| Diseases: |
Diabetes mellitus, type II
- [OMIM]
Insulin resistance |
| Mus musculus | |
| male | |
| homozygous db-/db- mouse from a C57BL/6 background | |
| BTO:0000131 blood plasma | |
| article | |
| Reference: | Altmaier E et al.(2008) Bioinformatics analysis of targeted metabolomics--uncovering old and new tales of diabetic mice under medication. Endocrinology 149: 3478-3489 [PMID: 18372322] |
Interaction Information:
| Comment | The diabetes phenotype reveals itself through high sugar concentrations and reduced concentrations of the glucogenic amino acids glycine, serine and alanine in diabetic mice when compared with the wild-type mice. This observation may be explained by an impaired uptake of glucose by insulin-resistant cells, which induces hepatic gluconeogenesis, a process that then consumes glucogenic amino acids to initiate the production of the glucose precursors pyruvate and 3-phosphoglycerate. |
|
Formal Description Interaction-ID: 19765 |
disease decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | The diabetes phenotype reveals itself through high sugar concentrations and reduced concentrations of the glucogenic amino acids glycine, serine and alanine in diabetic mice when compared with the wild-type mice. This observation may be explained by an impaired uptake of glucose by insulin-resistant cells, which induces hepatic gluconeogenesis, a process that then consumes glucogenic amino acids to initiate the production of the glucose precursors pyruvate and 3-phosphoglycerate. |
|
Formal Description Interaction-ID: 19767 |
disease decreases_quantity of drug/chemical compound |
| Comment | The diabetes phenotype reveals itself through high sugar concentrations and reduced concentrations of the glucogenic amino acids glycine, serine and alanine in diabetic mice when compared with the wild-type mice. This observation may be explained by an impaired uptake of glucose by insulin-resistant cells, which induces hepatic gluconeogenesis, a process that then consumes glucogenic amino acids to initiate the production of the glucose precursors pyruvate and 3-phosphoglycerate. |
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Formal Description Interaction-ID: 19773 |
disease decreases_quantity of drug/chemical compound |
| Comment | In contrast, plasma levels of the branched chain amino acids (BCAAs) leucine/isoleucine and valine are increased in diabetic mice. |
|
Formal Description Interaction-ID: 19774 |
disease increases_quantity of drug/chemical compound |
| Comment | In contrast, plasma levels of the branched chain amino acids (BCAAs) leucine/isoleucine and valine are increased in diabetic mice. |
|
Formal Description Interaction-ID: 19775 |
disease increases_quantity of drug/chemical compound |
| Comment | In contrast, plasma levels of the branched chain amino acids (BCAAs) leucine/isoleucine and valine are increased in diabetic mice. |
|
Formal Description Interaction-ID: 19777 |
disease increases_quantity of drug/chemical compound |
| Comment | Arginine levels in the diabetic mice are found to be decreased, a fact that is already known from experimental diabetic rats as well as from diabetic human patients. |
|
Formal Description Interaction-ID: 19779 |
disease decreases_quantity of drug/chemical compound |
| Comment | Ornithine levels are found to be increased in diabetic mice. This observation suggests that the activity of the arginase EC 3.5.3.1, which catalyzes the reaction from arginine to ornithine, is increased in diabetes. |
|
Formal Description Interaction-ID: 19783 |
disease increases_quantity of drug/chemical compound |
| Comment | An alternative interpretation, an increased degradation of arginine to citrulline by the nitric oxide synthase (EC 1.14.13.39), can be excluded because the concentrations of citrulline do not show any significant difference among the four mouse groups. |
|
Formal Description Interaction-ID: 19804 |
disease NOT affects_quantity of drug/chemical compound |
| Comment | The methylmalonyl carnitine (C3-DC-M) shows a significant increase. An explanation for the increase of this metabolite could be a ketosis induced in the diabetic mice because an increased glucose production at limited glucose use generally results in hyperglycemia. Besides C3-DC-M, plasma concentrations of three other short-chained acylcarnitines, namely hydroxyl propionylcarnitine [C3(OH)], pimeloylcarnitine (C7-DC), and butenoylcarnitine (C4:1), are also significantly increased in diabetic mice. |
|
Formal Description Interaction-ID: 19806 |
disease increases_quantity of drug/chemical compound Methylmalonylcarnitine |
| Comment | The methylmalonyl carnitine (C3-DC-M) shows a significant increase. An explanation for the increase of this metabolite could be a ketosis induced in the diabetic mice because an increased glucose production at limited glucose use generally results in hyperglycemia. Besides C3-DC-M, plasma concentrations of three other short-chained acylcarnitines, namely hydroxyl propionylcarnitine [C3(OH)], pimeloylcarnitine (C7-DC), and butenoylcarnitine (C4:1), are also significantly increased in diabetic mice. |
|
Formal Description Interaction-ID: 19812 |
disease increases_quantity of drug/chemical compound Hydroxypropionylcarnitine |
| Comment | The methylmalonyl carnitine (C3-DC-M) shows a significant increase. An explanation for the increase of this metabolite could be a ketosis induced in the diabetic mice because an increased glucose production at limited glucose use generally results in hyperglycemia. Besides C3-DC-M, plasma concentrations of three other short-chained acylcarnitines, namely hydroxyl propionylcarnitine [C3(OH)], pimeloylcarnitine (C7-DC), and butenoylcarnitine (C4:1), are also significantly increased in diabetic mice. |
|
Formal Description Interaction-ID: 19813 |
disease increases_quantity of drug/chemical compound Pimeloylcarnitine |
| Comment | The methylmalonyl carnitine (C3-DC-M) shows a significant increase. An explanation for the increase of this metabolite could be a ketosis induced in the diabetic mice because an increased glucose production at limited glucose use generally results in hyperglycemia. Besides C3-DC-M, plasma concentrations of three other short-chained acylcarnitines, namely hydroxyl propionylcarnitine [C3(OH)], pimeloylcarnitine (C7-DC), and butenoylcarnitine (C4:1), are also significantly increased in diabetic mice. |
|
Formal Description Interaction-ID: 19815 |
disease increases_quantity of drug/chemical compound Acylcarnitine C4:1 |
| Comment | Rosiglitazone treatment significantly reduces plasma concentrations of numerous acylcarnitines, in particular those of myristoyl- (C14), palmitoyl- (C16), and stearoylcarnitines (C18) with saturated side chains, and of hexadecenylcarnitine (C16:1), octadecenylcarnitine (C18:1), and octadecadienylcarnitine (C18:2) with unsaturated side chains, and this both in diabetic and in healthy mice. This observation agrees with the expected effect of rosiglitazone on reducing the concentrations of nonesterified fatty acids in individuals with type 2 diabetes because free long-chain fatty acids are metabolized to acylcarnitines when transported into mitochondria for beta-oxidation. |
|
Formal Description Interaction-ID: 19821 |
drug/chemical compound decreases_quantity of drug/chemical compound Tetradecanoylcarnitine |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Rosiglitazone treatment significantly reduces plasma concentrations of numerous acylcarnitines, in particular those of myristoyl- (C14), palmitoyl- (C16), and stearoylcarnitines (C18) with saturated side chains, and of hexadecenylcarnitine (C16:1), octadecenylcarnitine (C18:1), and octadecadienylcarnitine (C18:2) with unsaturated side chains, and this both in diabetic and in healthy mice. This observation agrees with the expected effect of rosiglitazone on reducing the concentrations of nonesterified fatty acids in individuals with type 2 diabetes because free long-chain fatty acids are metabolized to acylcarnitines when transported into mitochondria for beta-oxidation. |
|
Formal Description Interaction-ID: 19824 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Rosiglitazone treatment significantly reduces plasma concentrations of numerous acylcarnitines, in particular those of myristoyl- (C14), palmitoyl- (C16), and stearoylcarnitines (C18) with saturated side chains, and of hexadecenylcarnitine (C16:1), octadecenylcarnitine (C18:1), and octadecadienylcarnitine (C18:2) with unsaturated side chains, and this both in diabetic and in healthy mice. This observation agrees with the expected effect of rosiglitazone on reducing the concentrations of nonesterified fatty acids in individuals with type 2 diabetes because free long-chain fatty acids are metabolized to acylcarnitines when transported into mitochondria for beta-oxidation. |
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Formal Description Interaction-ID: 19825 |
drug/chemical compound decreases_quantity of drug/chemical compound Stearoylcarnitine |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Rosiglitazone treatment significantly reduces plasma concentrations of numerous acylcarnitines, in particular those of myristoyl- (C14), palmitoyl- (C16), and stearoylcarnitines (C18) with saturated side chains, and of hexadecenylcarnitine (C16:1), octadecenylcarnitine (C18:1), and octadecadienylcarnitine (C18:2) with unsaturated side chains, and this both in diabetic and in healthy mice. This observation agrees with the expected effect of rosiglitazone on reducing the concentrations of nonesterified fatty acids in individuals with type 2 diabetes because free long-chain fatty acids are metabolized to acylcarnitines when transported into mitochondria for beta-oxidation. |
|
Formal Description Interaction-ID: 19826 |
drug/chemical compound decreases_quantity of drug/chemical compound Acylcarnitine C16:1 |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Rosiglitazone treatment significantly reduces plasma concentrations of numerous acylcarnitines, in particular those of myristoyl- (C14), palmitoyl- (C16), and stearoylcarnitines (C18) with saturated side chains, and of hexadecenylcarnitine (C16:1), octadecenylcarnitine (C18:1), and octadecadienylcarnitine (C18:2) with unsaturated side chains, and this both in diabetic and in healthy mice. This observation agrees with the expected effect of rosiglitazone on reducing the concentrations of nonesterified fatty acids in individuals with type 2 diabetes because free long-chain fatty acids are metabolized to acylcarnitines when transported into mitochondria for beta-oxidation. |
|
Formal Description Interaction-ID: 19827 |
drug/chemical compound decreases_quantity of drug/chemical compound Acylcarnitine C18:1 |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Rosiglitazone treatment significantly reduces plasma concentrations of numerous acylcarnitines, in particular those of myristoyl- (C14), palmitoyl- (C16), and stearoylcarnitines (C18) with saturated side chains, and of hexadecenylcarnitine (C16:1), octadecenylcarnitine (C18:1), and octadecadienylcarnitine (C18:2) with unsaturated side chains, and this both in diabetic and in healthy mice. This observation agrees with the expected effect of rosiglitazone on reducing the concentrations of nonesterified fatty acids in individuals with type 2 diabetes because free long-chain fatty acids are metabolized to acylcarnitines when transported into mitochondria for beta-oxidation. |
|
Formal Description Interaction-ID: 19828 |
drug/chemical compound decreases_quantity of drug/chemical compound Acylcarnitine C18:2 |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Further observations, such as reduced concentrations of PCs and increased plasma levels of PI, PIP2, and PIP3, can be interpreted with respect to the aforementioned overall effect of rosiglitazone on the organism's lipid metabolism. PI, PIP2, and PIP3 additionally play an important role as second messengers, e.g. in the sensitizing of cells for glucose uptake by rosiglitazone treatment. |
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Formal Description Interaction-ID: 19831 |
drug/chemical compound decreases_quantity of drug/chemical compound PC ee C42:6 |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Further observations, such as reduced concentrations of PCs and increased plasma levels of PI, PIP2, and PIP3, can be interpreted with respect to the aforementioned overall effect of rosiglitazone on the organism's lipid metabolism. PI, PIP2, and PIP3 additionally play an important role as second messengers, e.g. in the sensitizing of cells for glucose uptake by rosiglitazone treatment. |
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Formal Description Interaction-ID: 19841 |
drug/chemical compound decreases_quantity of drug/chemical compound PC aa C40:5 |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Further observations, such as reduced concentrations of PCs and increased plasma levels of PI, PIP2, and PIP3, can be interpreted with respect to the aforementioned overall effect of rosiglitazone on the organism's lipid metabolism. PI, PIP2, and PIP3 additionally play an important role as second messengers, e.g. in the sensitizing of cells for glucose uptake by rosiglitazone treatment. |
|
Formal Description Interaction-ID: 19842 |
drug/chemical compound decreases_quantity of drug/chemical compound PC aa C40:6 |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Further observations, such as reduced concentrations of PCs and increased plasma levels of PI, PIP2, and PIP3, can be interpreted with respect to the aforementioned overall effect of rosiglitazone on the organism's lipid metabolism. PI, PIP2, and PIP3 additionally play an important role as second messengers, e.g. in the sensitizing of cells for glucose uptake by rosiglitazone treatment. |
|
Formal Description Interaction-ID: 19843 |
drug/chemical compound decreases_quantity of drug/chemical compound PC ee C42:5 |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Further observations, such as reduced concentrations of PCs and increased plasma levels of PI, PIP2, and PIP3, can be interpreted with respect to the aforementioned overall effect of rosiglitazone on the organism's lipid metabolism. PI, PIP2, and PIP3 additionally play an important role as second messengers, e.g. in the sensitizing of cells for glucose uptake by rosiglitazone treatment. |
|
Formal Description Interaction-ID: 19844 |
drug/chemical compound increases_quantity of drug/chemical compound PIP3 aa C42:3 |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Further observations, such as reduced concentrations of PCs and increased plasma levels of PI, PIP2, and PIP3, can be interpreted with respect to the aforementioned overall effect of rosiglitazone on the organism's lipid metabolism. PI, PIP2, and PIP3 additionally play an important role as second messengers, e.g. in the sensitizing of cells for glucose uptake by rosiglitazone treatment. |
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Formal Description Interaction-ID: 19845 |
drug/chemical compound increases_quantity of drug/chemical compound PIP2 aa C36:0 |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | Further observations, such as reduced concentrations of PCs and increased plasma levels of PI, PIP2, and PIP3, can be interpreted with respect to the aforementioned overall effect of rosiglitazone on the organism's lipid metabolism. PI, PIP2, and PIP3 additionally play an important role as second messengers, e.g. in the sensitizing of cells for glucose uptake by rosiglitazone treatment. |
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Formal Description Interaction-ID: 19846 |
drug/chemical compound increases_quantity of drug/chemical compound Glycerophosphatidylinositol |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | An additional outcome of the variance analysis is the possibility to find metabolites that are oppositely affected by treatment with rosiglitazone in healthy and diabetic mice. One interesting example is methylglutaryl carnitine (C5-M-DC), in which treatment with rosiglitazone increases plasma concentrations of C5-M-DC in diabetic mice, whereas it decreases these concentrations in healthy mice. |
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Formal Description Interaction-ID: 19847 |
drug/chemical compound increases_quantity of drug/chemical compound Methylglutarylcarnitine |
| Drugbank entries | Show/Hide entries for Rosiglitazone |
| Comment | An additional outcome of the variance analysis is the possibility to find metabolites that are oppositely affected by treatment with rosiglitazone in healthy and diabetic mice. One interesting example is methylglutaryl carnitine (C5-M-DC), in which treatment with rosiglitazone increases plasma concentrations of C5-M-DC in diabetic mice, whereas it decreases these concentrations in healthy mice. |
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Formal Description Interaction-ID: 19848 |
drug/chemical compound decreases_quantity of drug/chemical compound Methylglutarylcarnitine |
| Drugbank entries | Show/Hide entries for Rosiglitazone |