General Information:

Id: 3,471
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Obesity - [OMIM]
Mammalia
review
Reference: Bain JR et al.(2009) Metabolomics applied to diabetes research: moving from information to knowledge Diabetes 58: 2429-2443 [PMID: 19875619]

Interaction Information:

Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32299
Drugbank entries Show/Hide entries for PC
Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32301

gene/protein

PC

decreases_quantity of

drug/chemical compound

Pyruvate

Drugbank entries Show/Hide entries for PC
Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32302

gene/protein

PC

increases_quantity of

drug/chemical compound

Oxaloacetate

Drugbank entries Show/Hide entries for PC
Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32305

affects_quantity of

drug/chemical compound

Oxaloacetate

Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32306

increases_quantity of

drug/chemical compound

Citrate

Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32307

increases_quantity of

drug/chemical compound

Isocitrate

Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32308

gene/protein

SLC25A1

increases_transport of

drug/chemical compound

Citrate

out of the mitochondria into the cytosol
Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32309

gene/protein

SLC25A1

increases_transport of

drug/chemical compound

Isocitrate

out of the mitochondria into the cytosol
Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32310

gene/protein

ACO1

decreases_quantity of

drug/chemical compound

Citrate

Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32311

gene/protein

ACO1

increases_quantity of

drug/chemical compound

Isocitrate

Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32312

decreases_quantity of

drug/chemical compound

Isocitrate

Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32313

increases_quantity of

drug/chemical compound

2-Oxoglutarate

Comment Application of NMR and MS-based tools led to the discovery of a critical link between pyruvate carboxylase (PC)-mediated pyruvate exchange with tricarboxylic acid (TCA) cycle intermediates (pyruvate cycling) and glucose-stimulated insulin secretion (GSIS) and demonstration that these pathways are dysregulated in lipid-cultured and dysfunctional beta-cells. One important pathway appears to involve export of citrate and/or isocitrate from the mitochondria via the citrate/isocitrate carrier (CIC) and subsequent conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by the cytosolic NAPD-dependent isoform of isocitrate dehydrogenase (ICDc).
Formal Description
Interaction-ID: 32314
Comment Chronic exposure of muscle to elevated lipids in vitro, or in vivo as a consequence of overnutrition, resulted in an increase rather than a decrease in expression of genes of fatty acid beta-oxidation. This lipid-induced upregulation of the enzymatic machinery for beta-oxidation of fatty acids in muscle was not coordinated with upregulation of downstream metabolic pathways such as the TCA cycle and electron transport chain. This resulted in incomplete metabolism of fatty acids in the beta-oxidation pathway, as reflected by broad-scale accumulation of mitochondrial lipid metabolites (acylcarnitines) and a simultaneous decrease in the levels of TCA cycle intermediates.
Formal Description
Interaction-ID: 32351

environment

overnutrition

increases_activity of

process

incomplete fatty acid beta-oxidation

Comment Chronic exposure of muscle to elevated lipids in vitro, or in vivo as a consequence of overnutrition, resulted in an increase rather than a decrease in expression of genes of fatty acid beta-oxidation. This lipid-induced upregulation of the enzymatic machinery for beta-oxidation of fatty acids in muscle was not coordinated with upregulation of downstream metabolic pathways such as the TCA cycle and electron transport chain. This resulted in incomplete metabolism of fatty acids in the beta-oxidation pathway, as reflected by broad-scale accumulation of mitochondrial lipid metabolites (acylcarnitines) and a simultaneous decrease in the levels of TCA cycle intermediates.
Formal Description
Interaction-ID: 32352

environment

overnutrition

NOT increases_activity of

Comment Chronic exposure of muscle to elevated lipids in vitro, or in vivo as a consequence of overnutrition, resulted in an increase rather than a decrease in expression of genes of fatty acid beta-oxidation. This lipid-induced upregulation of the enzymatic machinery for beta-oxidation of fatty acids in muscle was not coordinated with upregulation of downstream metabolic pathways such as the TCA cycle and electron transport chain. This resulted in incomplete metabolism of fatty acids in the beta-oxidation pathway, as reflected by broad-scale accumulation of mitochondrial lipid metabolites (acylcarnitines) and a simultaneous decrease in the levels of TCA cycle intermediates.
Formal Description
Interaction-ID: 32353

process

incomplete fatty acid beta-oxidation

increases_quantity of

drug/chemical compound

Acylcarnitine

Comment Exercising of obese mice normalizes the elevated acylcarnitines in muscle and restores insulin sensitivity and glucose tolerance.
Formal Description
Interaction-ID: 32354

environment

exercise

decreases_quantity of

drug/chemical compound

Acylcarnitine

Comment A study used LC-MS-MS to profile lipids secreted from the small intestine in response to ingestion of fat. This approach showed an increase in N-acylphosphatidylethanolamines (NAPEs) in the circulation. Systemic infusion of the most abundant NAPE decreased food intake in rats, an effect that could not be ascribed to taste aversion. The authors also demonstrated that systemically administered NAPE enters the brain and accumulates in the hypothalamus. Chronic administration of NAPEs reduces food intake and decreases body weight.
Formal Description
Interaction-ID: 32358

environment

high-fat diet

increases_quantity of

drug/chemical compound

N-Acylphosphatidylethanolamine

Comment A study used LC-MS-MS to profile lipids secreted from the small intestine in response to ingestion of fat. This approach showed an increase in N-acylphosphatidylethanolamines (NAPEs) in the circulation. Systemic infusion of the most abundant NAPE decreased food intake in rats, an effect that could not be ascribed to taste aversion. The authors also demonstrated that systemically administered NAPE enters the brain and accumulates in the hypothalamus. Chronic administration of NAPEs reduces food intake and decreases body weight.
Formal Description
Interaction-ID: 32359

environment

high-fat diet

increases_quantity of

drug/chemical compound

N-Acylphosphatidylethanolamine

Comment A study used LC-MS-MS to profile lipids secreted from the small intestine in response to ingestion of fat. This approach showed an increase in N-acylphosphatidylethanolamines (NAPEs) in the circulation. Systemic infusion of the most abundant NAPE decreased food intake in rats, an effect that could not be ascribed to taste aversion. The authors also demonstrated that systemically administered NAPE enters the brain and accumulates in the hypothalamus. Chronic administration of NAPEs reduces food intake and decreases body weight.
Formal Description
Interaction-ID: 32360

drug/chemical compound

N-Acylphosphatidylethanolamine

increases_activity of

Comment Nuclear receptors, including the family of PPAR-alpha, -delta, and -gamma, have emerged as important mediators of insulin sensitivity. 1H-NMR-, LC-MS-, and GC-MS-based methods were used to compare PPAR-alpha null and wild-type mice. The authors reported decreases in glucose, glutamine, and alanine levels and an increase in lactate, suggesting an increase in utilization of glucose and amino acids, as might be predicted from the known effects of PPAR-alpha to promote the opposing pathways of beta-oxidation, ketogenesis, and gluconeogenesis.
Formal Description
Interaction-ID: 32365

gene/protein

PPARA

affects_quantity of

drug/chemical compound

Glucose

Drugbank entries Show/Hide entries for PPARA
Comment Nuclear receptors, including the family of PPAR-alpha, -delta, and -gamma, have emerged as important mediators of insulin sensitivity. 1H-NMR-, LC-MS-, and GC-MS-based methods were used to compare PPAR-alpha null and wild-type mice. The authors reported decreases in glucose, glutamine, and alanine levels and an increase in lactate, suggesting an increase in utilization of glucose and amino acids, as might be predicted from the known effects of PPAR-alpha to promote the opposing pathways of beta-oxidation, ketogenesis, and gluconeogenesis.
Formal Description
Interaction-ID: 32378

gene/protein

PPARA

affects_quantity of

drug/chemical compound

Glutamine

Drugbank entries Show/Hide entries for PPARA
Comment Nuclear receptors, including the family of PPAR-alpha, -delta, and -gamma, have emerged as important mediators of insulin sensitivity. 1H-NMR-, LC-MS-, and GC-MS-based methods were used to compare PPAR-alpha null and wild-type mice. The authors reported decreases in glucose, glutamine, and alanine levels and an increase in lactate, suggesting an increase in utilization of glucose and amino acids, as might be predicted from the known effects of PPAR-alpha to promote the opposing pathways of beta-oxidation, ketogenesis, and gluconeogenesis.
Formal Description
Interaction-ID: 32382

gene/protein

PPARA

affects_quantity of

drug/chemical compound

Alanine

Drugbank entries Show/Hide entries for PPARA
Comment Nuclear receptors, including the family of PPAR-alpha, -delta, and -gamma, have emerged as important mediators of insulin sensitivity. 1H-NMR-, LC-MS-, and GC-MS-based methods were used to compare PPAR-alpha null and wild-type mice. The authors reported decreases in glucose, glutamine, and alanine levels and an increase in lactate, suggesting an increase in utilization of glucose and amino acids, as might be predicted from the known effects of PPAR-alpha to promote the opposing pathways of beta-oxidation, ketogenesis, and gluconeogenesis.
Formal Description
Interaction-ID: 32385

gene/protein

PPARA

affects_quantity of

drug/chemical compound

Lactate

Drugbank entries Show/Hide entries for PPARA
Comment Nuclear receptors, including the family of PPAR-alpha, -delta, and -gamma, have emerged as important mediators of insulin sensitivity. 1H-NMR-, LC-MS-, and GC-MS-based methods were used to compare PPAR-alpha null and wild-type mice. The authors reported decreases in glucose, glutamine, and alanine levels and an increase in lactate, suggesting an increase in utilization of glucose and amino acids, as might be predicted from the known effects of PPAR-alpha to promote the opposing pathways of beta-oxidation, ketogenesis, and gluconeogenesis.
Formal Description
Interaction-ID: 32387

gene/protein

PPARA

affects_activity of

Drugbank entries Show/Hide entries for PPARA
Comment Nuclear receptors, including the family of PPAR-alpha, -delta, and -gamma, have emerged as important mediators of insulin sensitivity. 1H-NMR-, LC-MS-, and GC-MS-based methods were used to compare PPAR-alpha null and wild-type mice. The authors reported decreases in glucose, glutamine, and alanine levels and an increase in lactate, suggesting an increase in utilization of glucose and amino acids, as might be predicted from the known effects of PPAR-alpha to promote the opposing pathways of beta-oxidation, ketogenesis, and gluconeogenesis.
Formal Description
Interaction-ID: 32388

gene/protein

PPARA

affects_activity of

Drugbank entries Show/Hide entries for PPARA
Comment Nuclear receptors, including the family of PPAR-alpha, -delta, and -gamma, have emerged as important mediators of insulin sensitivity. 1H-NMR-, LC-MS-, and GC-MS-based methods were used to compare PPAR-alpha null and wild-type mice. The authors reported decreases in glucose, glutamine, and alanine levels and an increase in lactate, suggesting an increase in utilization of glucose and amino acids, as might be predicted from the known effects of PPAR-alpha to promote the opposing pathways of beta-oxidation, ketogenesis, and gluconeogenesis.
Formal Description
Interaction-ID: 32390

gene/protein

PPARA

affects_activity of

process

gluconeogenesis

Drugbank entries Show/Hide entries for PPARA
Comment Targeted GC-MS and LC-MS-MS analysis has provided deeper insights by showing that PPAR-alpha knockout results in fasting hypoglycemia accompanied by depletion of TCA cycle intermediates and free carnitine and short-chain acylcarnitines, as well as accumulation of long-chain acyl CoAs in skeletal muscle.
Formal Description
Interaction-ID: 32391

gene/protein

PPARA

affects_activity of

phenotype

hypoglycemia

after fasting
Drugbank entries Show/Hide entries for PPARA
Comment Targeted GC-MS and LC-MS-MS analysis has provided deeper insights by showing that PPAR-alpha knockout results in fasting hypoglycemia accompanied by depletion of TCA cycle intermediates and free carnitine and short-chain acylcarnitines, as well as accumulation of long-chain acyl CoAs in skeletal muscle.
Formal Description
Interaction-ID: 32393

gene/protein

PPARA

affects_activity of

Drugbank entries Show/Hide entries for PPARA
Comment Targeted GC-MS and LC-MS-MS analysis has provided deeper insights by showing that PPAR-alpha knockout results in fasting hypoglycemia accompanied by depletion of TCA cycle intermediates and free carnitine and short-chain acylcarnitines, as well as accumulation of long-chain acyl CoAs in skeletal muscle.
Formal Description
Interaction-ID: 32394

gene/protein

PPARA

affects_quantity of

drug/chemical compound

Carnitine

Drugbank entries Show/Hide entries for PPARA
Comment Targeted GC-MS and LC-MS-MS analysis has provided deeper insights by showing that PPAR-alpha knockout results in fasting hypoglycemia accompanied by depletion of TCA cycle intermediates and free carnitine and short-chain acylcarnitines, as well as accumulation of long-chain acyl CoAs in skeletal muscle.
Formal Description
Interaction-ID: 32397

gene/protein

PPARA

affects_quantity of

drug/chemical compound

Short-chain acylcarnitine

Drugbank entries Show/Hide entries for PPARA
Comment Targeted GC-MS and LC-MS-MS analysis has provided deeper insights by showing that PPAR-alpha knockout results in fasting hypoglycemia accompanied by depletion of TCA cycle intermediates and free carnitine and short-chain acylcarnitines, as well as accumulation of long-chain acyl CoAs in skeletal muscle.
Formal Description
Interaction-ID: 32400

gene/protein

PPARA

affects_quantity of

drug/chemical compound

Long-chain acyl-CoA

Drugbank entries Show/Hide entries for PPARA
Comment The amino acid glutamine acts through alanine:glyoxylate aminotransferase (Agxt) and arginase 1 (Arg1) to affect phosphoenolpyruvate carboxykinase (Pck1) expression. Consistent with this predicted network, glutamine addition to primary hepatocytes causes strong upregulation of Agxt, Arg1, and PEPCK. Moreover, glutamine and PEPCK mRNA levels are reduced with obesity in diabetes-resistant B6-ob/ob mice but increased in liver of diabetes-susceptible BTBR-ob/ob animals.
Formal Description
Interaction-ID: 32404

drug/chemical compound

Glutamine

affects_expression of

gene/protein

PCK1

via AGXT and ARG1
Drugbank entries Show/Hide entries for PCK1
Comment The amino acid glutamine acts through alanine:glyoxylate aminotransferase (Agxt) and arginase 1 (Arg1) to affect phosphoenolpyruvate carboxykinase (Pck1) expression. Consistent with this predicted network, glutamine addition to primary hepatocytes causes strong upregulation of Agxt, Arg1, and PEPCK. Moreover, glutamine and PEPCK mRNA levels are reduced with obesity in diabetes-resistant B6-ob/ob mice but increased in liver of diabetes-susceptible BTBR-ob/ob animals.
Formal Description
Interaction-ID: 32440

drug/chemical compound

Glutamine

increases_expression of

gene/protein

AGXT

Drugbank entries Show/Hide entries for AGXT
Comment The amino acid glutamine acts through alanine:glyoxylate aminotransferase (Agxt) and arginase 1 (Arg1) to affect phosphoenolpyruvate carboxykinase (Pck1) expression. Consistent with this predicted network, glutamine addition to primary hepatocytes causes strong upregulation of Agxt, Arg1, and PEPCK. Moreover, glutamine and PEPCK mRNA levels are reduced with obesity in diabetes-resistant B6-ob/ob mice but increased in liver of diabetes-susceptible BTBR-ob/ob animals.
Formal Description
Interaction-ID: 32441

drug/chemical compound

Glutamine

increases_expression of

gene/protein

ARG1

Drugbank entries Show/Hide entries for ARG1
Comment The amino acid glutamine acts through alanine:glyoxylate aminotransferase (Agxt) and arginase 1 (Arg1) to affect phosphoenolpyruvate carboxykinase (Pck1) expression. Consistent with this predicted network, glutamine addition to primary hepatocytes causes strong upregulation of Agxt, Arg1, and PEPCK. Moreover, glutamine and PEPCK mRNA levels are reduced with obesity in diabetes-resistant B6-ob/ob mice but increased in liver of diabetes-susceptible BTBR-ob/ob animals.
Formal Description
Interaction-ID: 32442

drug/chemical compound

Glutamine

increases_expression of

gene/protein

PCK1

Drugbank entries Show/Hide entries for PCK1
Comment The amino acid glutamine acts through alanine:glyoxylate aminotransferase (Agxt) and arginase 1 (Arg1) to affect phosphoenolpyruvate carboxykinase (Pck1) expression. Consistent with this predicted network, glutamine addition to primary hepatocytes causes strong upregulation of Agxt, Arg1, and PEPCK. Moreover, glutamine and PEPCK mRNA levels are reduced with obesity in diabetes-resistant B6-ob/ob mice but increased in liver of diabetes-susceptible BTBR-ob/ob animals.
Formal Description
Interaction-ID: 32443

gene/protein

PCK1

affects_activity of

Drugbank entries Show/Hide entries for PCK1
Comment The amino acid glutamine acts through alanine:glyoxylate aminotransferase (Agxt) and arginase 1 (Arg1) to affect phosphoenolpyruvate carboxykinase (Pck1) expression. Consistent with this predicted network, glutamine addition to primary hepatocytes causes strong upregulation of Agxt, Arg1, and PEPCK. Moreover, glutamine and PEPCK mRNA levels are reduced with obesity in diabetes-resistant B6-ob/ob mice but increased in liver of diabetes-susceptible BTBR-ob/ob animals.
Formal Description
Interaction-ID: 32444

drug/chemical compound

Glutamine

affects_activity of

Comment Profiling of obese versus lean humans revealed a branched-chain amino acid (BCAA)-related metabolite signature that differentiates the two groups, is suggestive of increased catabolism of BCAA, and correlates with insulin resistance. The signature includes several metabolites that are byproducts of BCAA catabolism, such as glutamate, alpha-ketoglutarate, C3 acylcarnitine (propionylcarnitine), and C5 acylcarnitines (alpha-methylbutyryl and isovalerylcarnitines).
Formal Description
Interaction-ID: 32453

disease

Obesity

increases_activity of

Comment Profiling of obese versus lean humans revealed a branched-chain amino acid (BCAA)-related metabolite signature that differentiates the two groups, is suggestive of increased catabolism of BCAA, and correlates with insulin resistance. The signature includes several metabolites that are byproducts of BCAA catabolism, such as glutamate, alpha-ketoglutarate, C3 acylcarnitine (propionylcarnitine), and C5 acylcarnitines (alpha-methylbutyryl and isovalerylcarnitines).
Formal Description
Interaction-ID: 32455

affects_activity of

disease

Insulin resistance

Comment Profiling of obese versus lean humans revealed a branched-chain amino acid (BCAA)-related metabolite signature that differentiates the two groups, is suggestive of increased catabolism of BCAA, and correlates with insulin resistance. The signature includes several metabolites that are byproducts of BCAA catabolism, such as glutamate, alpha-ketoglutarate, C3 acylcarnitine (propionylcarnitine), and C5 acylcarnitines (alpha-methylbutyryl and isovalerylcarnitines).
Formal Description
Interaction-ID: 32457

affects_quantity of

drug/chemical compound

Glutamine

Comment Profiling of obese versus lean humans revealed a branched-chain amino acid (BCAA)-related metabolite signature that differentiates the two groups, is suggestive of increased catabolism of BCAA, and correlates with insulin resistance. The signature includes several metabolites that are byproducts of BCAA catabolism, such as glutamate, alpha-ketoglutarate, C3 acylcarnitine (propionylcarnitine), and C5 acylcarnitines (alpha-methylbutyryl and isovalerylcarnitines).
Formal Description
Interaction-ID: 32466

affects_quantity of

drug/chemical compound

2-Oxoglutarate

Comment Profiling of obese versus lean humans revealed a branched-chain amino acid (BCAA)-related metabolite signature that differentiates the two groups, is suggestive of increased catabolism of BCAA, and correlates with insulin resistance. The signature includes several metabolites that are byproducts of BCAA catabolism, such as glutamate, alpha-ketoglutarate, C3 acylcarnitine (propionylcarnitine), and C5 acylcarnitines (alpha-methylbutyryl and isovalerylcarnitines).
Formal Description
Interaction-ID: 32472

affects_quantity of

drug/chemical compound

Propanoylcarnitine

Comment Profiling of obese versus lean humans revealed a branched-chain amino acid (BCAA)-related metabolite signature that differentiates the two groups, is suggestive of increased catabolism of BCAA, and correlates with insulin resistance. The signature includes several metabolites that are byproducts of BCAA catabolism, such as glutamate, alpha-ketoglutarate, C3 acylcarnitine (propionylcarnitine), and C5 acylcarnitines (alpha-methylbutyryl and isovalerylcarnitines).
Formal Description
Interaction-ID: 32473

affects_quantity of

drug/chemical compound

Alpha-methylbutyrylcarnitine

Comment Profiling of obese versus lean humans revealed a branched-chain amino acid (BCAA)-related metabolite signature that differentiates the two groups, is suggestive of increased catabolism of BCAA, and correlates with insulin resistance. The signature includes several metabolites that are byproducts of BCAA catabolism, such as glutamate, alpha-ketoglutarate, C3 acylcarnitine (propionylcarnitine), and C5 acylcarnitines (alpha-methylbutyryl and isovalerylcarnitines).
Formal Description
Interaction-ID: 32475

affects_quantity of

drug/chemical compound

Isovalerylcarnitine

Comment Targeted profiling has also been applied during an oral glucose tolerance test in human subjects. In two small independent groups of normal non-insulin-resistant individuals (n 22 and 25), glucose ingestion caused significant changes in 18 metabolites (other than glucose) among 191 measured, including some that are involved in pathways not known to be affected by a glucose load (bile acids and purine degradation products).
Formal Description
Interaction-ID: 32476

drug/chemical compound

Glucose

affects_activity of

Comment Targeted profiling has also been applied during an oral glucose tolerance test in human subjects. In two small independent groups of normal non-insulin-resistant individuals (n 22 and 25), glucose ingestion caused significant changes in 18 metabolites (other than glucose) among 191 measured, including some that are involved in pathways not known to be affected by a glucose load (bile acids and purine degradation products).
Formal Description
Interaction-ID: 32478

drug/chemical compound

Glucose

affects_activity of

Comment 6 of the 18 metabolites identified as 'glucose responsive' in the studies of normal subjects were found to correlate significantly with fasting insulin levels, used as a surrogate of insulin sensitivity. Among these were all three branched-chain amino acids, lactate, and beta-hydroxybutyrate.
Formal Description
Interaction-ID: 32481

drug/chemical compound

Glucose

affects_quantity of

drug/chemical compound

Leucine

Comment 6 of the 18 metabolites identified as 'glucose responsive' in the studies of normal subjects were found to correlate significantly with fasting insulin levels, used as a surrogate of insulin sensitivity. Among these were all three branched-chain amino acids, lactate, and beta-hydroxybutyrate.
Formal Description
Interaction-ID: 32483

drug/chemical compound

Glucose

affects_quantity of

drug/chemical compound

Isoleucine

Comment 6 of the 18 metabolites identified as 'glucose responsive' in the studies of normal subjects were found to correlate significantly with fasting insulin levels, used as a surrogate of insulin sensitivity. Among these were all three branched-chain amino acids, lactate, and beta-hydroxybutyrate.
Formal Description
Interaction-ID: 32484

drug/chemical compound

Glucose

affects_quantity of

drug/chemical compound

Valine

Comment 6 of the 18 metabolites identified as 'glucose responsive' in the studies of normal subjects were found to correlate significantly with fasting insulin levels, used as a surrogate of insulin sensitivity. Among these were all three branched-chain amino acids, lactate, and beta-hydroxybutyrate.
Formal Description
Interaction-ID: 32485

drug/chemical compound

Glucose

affects_quantity of

drug/chemical compound

Lactate

Comment 6 of the 18 metabolites identified as 'glucose responsive' in the studies of normal subjects were found to correlate significantly with fasting insulin levels, used as a surrogate of insulin sensitivity. Among these were all three branched-chain amino acids, lactate, and beta-hydroxybutyrate.
Formal Description
Interaction-ID: 32486

drug/chemical compound

Glucose

affects_quantity of

drug/chemical compound

(R)-3-Hydroxybutanoate