General Information:

Id: 5,152
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Nephropathy, diabetic
Mus musculus
male
article
Reference: Kim MY et al.(2013) Resveratrol prevents renal lipotoxicity and inhibits mesangial cell glucotoxicity in a manner dependent on the AMPK-SIRT1-PGC1alpha axis in db/db mice Diabetologia 56: 204-217 [PMID: 23090186]

Interaction Information:

Comment The db/db mice treated with resveratrol had decreased albuminuria.
Formal Description
Interaction-ID: 50388

drug/chemical compound

Resveratrol

decreases_activity of

phenotype

albuminuria

in db/db mice
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Comment Resveratrol ameliorated glomerular matrix expansion and inflammation. The levels of the pro-fibrotic growth factor TGF-beta1 and associated extracellular matrix type IV collagen and inflammatory cell glomerular infiltration were significantly increased in the db/db mice. All of the diabetes-induced renal phenotypic changes and inflammation seen in the db/db mice were reversed by resveratrol treatment. The significantly increased production of type IV collagen in db/db mice was reversed by resveratrol treatment.
Formal Description
Interaction-ID: 50390

drug/chemical compound

Resveratrol

decreases_activity of

in kidney; in db/db mice
Drugbank entries Show/Hide entries for Resveratrol
Comment Resveratrol ameliorated glomerular matrix expansion and inflammation. The levels of the pro-fibrotic growth factor TGF-beta1 and associated extracellular matrix type IV collagen and inflammatory cell glomerular infiltration were significantly increased in the db/db mice. All of the diabetes-induced renal phenotypic changes and inflammation seen in the db/db mice were reversed by resveratrol treatment. The significantly increased production of type IV collagen in db/db mice was reversed by resveratrol treatment.
Formal Description
Interaction-ID: 50391

drug/chemical compound

Resveratrol

decreases_activity of

in kidney; in db/db mice
Drugbank entries Show/Hide entries for Resveratrol
Comment Resveratrol ameliorated glomerular matrix expansion and inflammation. The levels of the pro-fibrotic growth factor TGF-beta1 and associated extracellular matrix type IV collagen and inflammatory cell glomerular infiltration were significantly increased in the db/db mice. All of the diabetes-induced renal phenotypic changes and inflammation seen in the db/db mice were reversed by resveratrol treatment. The significantly increased production of type IV collagen in db/db mice was reversed by resveratrol treatment.
Formal Description
Interaction-ID: 50393

drug/chemical compound

Resveratrol

decreases_quantity of

complex/PPI

Collagen IV

in kidney; in db/db mice
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Comment Resveratrol lowered the non-esterified fatty acids (NEFA) and triacylglycerol content of the kidney.
Formal Description
Interaction-ID: 50398

drug/chemical compound

Resveratrol

decreases_quantity of

drug/chemical compound

Fatty acid

in kidney; in db/db mice
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Comment Resveratrol lowered the non-esterified fatty acids (NEFA) and triacylglycerol content of the kidney.
Formal Description
Interaction-ID: 50400

drug/chemical compound

Resveratrol

decreases_quantity of

drug/chemical compound

Triacylglycerol

in kidney; in db/db mice
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Comment Resveratrol lowered the non-esterified fatty acids (NEFA) and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK (at Thr172 of the alpha chain) and the activation of SIRT1-PGC-1alpha signalling and of the key downstream effectors, the PPARalpha-oestrogen-related receptor (ERR)-1alpha-sterol regulatory element-binding protein 1 (SREBP1).
Formal Description
Interaction-ID: 50401

drug/chemical compound

Resveratrol

increases_activity of

complex/PPI

AMPK

in kidney; in db/db mice, via phosphorylation at Thr172 of AMPK alpha chain
Drugbank entries Show/Hide entries for Resveratrol
Comment Resveratrol lowered the non-esterified fatty acids (NEFA) and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK (at Thr172 of the alpha chain) and the activation of SIRT1-PGC-1alpha signalling and of the key downstream effectors, the PPARalpha-oestrogen-related receptor (ERR)-1alpha-sterol regulatory element-binding protein 1 (SREBP1).
Formal Description
Interaction-ID: 50404

drug/chemical compound

Resveratrol

increases_activity of

gene/protein

SIRT1

in kidney; in db/db mice
Drugbank entries Show/Hide entries for Resveratrol
Comment Resveratrol lowered the non-esterified fatty acids (NEFA) and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK (at Thr172 of the alpha chain) and the activation of SIRT1-PGC-1alpha signalling and of the key downstream effectors, the PPARalpha-oestrogen-related receptor (ERR)-1alpha-sterol regulatory element-binding protein 1 (SREBP1).
Formal Description
Interaction-ID: 50405

drug/chemical compound

Resveratrol

increases_activity of

gene/protein

PPARGC1A

in kidney; in db/db mice, via increased acetylated Lys-PGC-1alpha levels
Drugbank entries Show/Hide entries for Resveratrol
Comment Resveratrol lowered the non-esterified fatty acids (NEFA) and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK (at Thr172 of the alpha chain) and the activation of SIRT1-PGC-1alpha signalling and of the key downstream effectors, the PPARalpha-oestrogen-related receptor (ERR)-1alpha-sterol regulatory element-binding protein 1 (SREBP1).
Formal Description
Interaction-ID: 50408

drug/chemical compound

Resveratrol

increases_activity of

gene/protein

SREBF1

in kidney; in db/db mice
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Comment The phosphatidylinositol-3 kinase (PI3K) level and activity, as well as the phospho-Akt Ser473/total Akt ratio were significantly increased in db/db mice. Resveratrol treatment of db/db mice decreased the PI3K level and phospho-Ser473 Akt /total Akt ratio compared with the levels of the db/db mice.
Formal Description
Interaction-ID: 50409

drug/chemical compound

Resveratrol

decreases_activity of

complex/PPI

Phosphatidylinositol 3-kinase

in kidney; in db/db mice
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Comment The phosphatidylinositol-3 kinase (PI3K) level and activity, as well as the phospho-Akt Ser473/total Akt ratio were significantly increased in db/db mice. Resveratrol treatment of db/db mice decreased the PI3K level and phospho-Ser473 Akt /total Akt ratio compared with the levels of the db/db mice.
Formal Description
Interaction-ID: 50411

drug/chemical compound

Resveratrol

decreases_activity of

gene/protein

AKT1

in kidney; in db/db mice, via decreased phosphorylation at Ser473
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Comment Increases in the renal oxidative DNA damage and lipid peroxidation, as reflected by the renal and urinary 8-hydroxy-deoxyguanosine (8-OH-dG) and urinary 8-isoprostane concentrations, respectively, were observed in db/db mice. Resveratrol reversed the increase in renal apoptotic cells and oxidative stress, as reflected by renal 8-OH-dG, urinary 8-OH-dG and isoprostane concentrations.
Formal Description
Interaction-ID: 50412

drug/chemical compound

Resveratrol

decreases_activity of

in kidney; in db/db mice
Drugbank entries Show/Hide entries for Resveratrol
Comment Increases in the renal oxidative DNA damage and lipid peroxidation, as reflected by the renal and urinary 8-hydroxy-deoxyguanosine (8-OH-dG) and urinary 8-isoprostane concentrations, respectively, were observed in db/db mice. Resveratrol reversed the increase in renal apoptotic cells and oxidative stress, as reflected by renal 8-OH-dG, urinary 8-OH-dG and isoprostane concentrations.
Formal Description
Interaction-ID: 50414

drug/chemical compound

Resveratrol

decreases_quantity of

drug/chemical compound

8-Hydroxy-deoxyguanosine

in kidney, in urine; in db/db mice
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Comment Increases in the renal oxidative DNA damage and lipid peroxidation, as reflected by the renal and urinary 8-hydroxy-deoxyguanosine (8-OH-dG) and urinary 8-isoprostane concentrations, respectively, were observed in db/db mice. Resveratrol reversed the increase in renal apoptotic cells and oxidative stress, as reflected by renal 8-OH-dG, urinary 8-OH-dG and isoprostane concentrations.
Formal Description
Interaction-ID: 50416

drug/chemical compound

Resveratrol

decreases_quantity of

drug/chemical compound

8-Isoprostane

in urine; in db/db mice
Drugbank entries Show/Hide entries for Resveratrol
Comment Previous studies have shown that FOXO3a activation has an anti-stress and anti-apoptotic action via the enhancement of BCL-2 activity and the downregulation of pro-apoptotic BCL-2-associated X protein (BAX) activity. An increased level of phospho-FOXO3a Ser253 was noted in db/db mice. Resveratrol decreased the activity of class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production.
Formal Description
Interaction-ID: 50418

drug/chemical compound

Resveratrol

decreases_phosphorylation of

mRNA/protein variant

FOXO3a

in kidney; in db/db mice, at Ser253
Drugbank entries Show/Hide entries for Resveratrol
Comment Previous studies have shown that FOXO3a activation has an anti-stress and anti-apoptotic action via the enhancement of BCL-2 activity and the downregulation of pro-apoptotic BCL-2-associated X protein (BAX) activity. An increased level of phospho-FOXO3a Ser253 was noted in db/db mice. Resveratrol decreased the activity of class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production.
Formal Description
Interaction-ID: 50426

drug/chemical compound

Resveratrol

increases_quantity of

gene/protein

BCL2

in kidney; in db/db mice
Drugbank entries Show/Hide entries for Resveratrol or BCL2
Comment Previous studies have shown that FOXO3a activation has an anti-stress and anti-apoptotic action via the enhancement of BCL-2 activity and the downregulation of pro-apoptotic BCL-2-associated X protein (BAX) activity. An increased level of phospho-FOXO3a Ser253 was noted in db/db mice. Resveratrol decreased the activity of class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production.
Formal Description
Interaction-ID: 50428

drug/chemical compound

Resveratrol

decreases_quantity of

gene/protein

BAX

in kidney; in db/db mice
Drugbank entries Show/Hide entries for Resveratrol
Comment Previous studies have shown that FOXO3a activation has an anti-stress and anti-apoptotic action via the enhancement of BCL-2 activity and the downregulation of pro-apoptotic BCL-2-associated X protein (BAX) activity. An increased level of phospho-FOXO3a Ser253 was noted in db/db mice. Resveratrol decreased the activity of class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production.
Formal Description
Interaction-ID: 50430

drug/chemical compound

Resveratrol

increases_quantity of

gene/protein

SOD1

in kidney; in db/db mice
Drugbank entries Show/Hide entries for Resveratrol or SOD1
Comment Previous studies have shown that FOXO3a activation has an anti-stress and anti-apoptotic action via the enhancement of BCL-2 activity and the downregulation of pro-apoptotic BCL-2-associated X protein (BAX) activity. An increased level of phospho-FOXO3a Ser253 was noted in db/db mice. Resveratrol decreased the activity of class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production.
Formal Description
Interaction-ID: 50431

drug/chemical compound

Resveratrol

increases_quantity of

gene/protein

SOD2

in kidney; in db/db mice
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Comment The results suggest that resveratrol prevents diabetic nephropathy in db/db mice by the phosphorylation of AMPK and activation of SIRT1-PGC-1alpha signalling, which appear to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.
Formal Description
Interaction-ID: 50432

drug/chemical compound

Resveratrol

decreases_activity of

disease

Nephropathy, diabetic

in db/db mice
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