General Information:

Id: 824 (click here to show other Interactions for entry)
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Obesity - [OMIM]
Mammalia
review
Reference: Sugden MC et al.(2010) PPAR control: its SIRTainly as easy as PGC J. Endocrinol. 2: 93-104 [PMID: 19770177]

Interaction Information:

Comment SIRT1-mediated deacetylation activates PGC-1alpha, while acetylation by GCN5 inhibits PGC-1alpha-directed gene expression.
Formal Description
Interaction-ID: 4790

gene/protein

SIRT1

decreases_acetylation of

gene/protein

PPARGC1A

Comment SIRT1-mediated deacetylation activates PGC-1alpha, while acetylation by GCN5 inhibits PGC-1alpha-directed gene expression.
Formal Description
Interaction-ID: 4791

gene/protein

SIRT1

increases_activity of

gene/protein

PPARGC1A

Comment Protein deacetylase SIRT1 (the mammalian Sir2 ortholog) deacetylates a number of nonhistone targets including PGC-1alpha and PGC-1beta, with activation of both cofactors.
Formal Description
Interaction-ID: 4816

gene/protein

SIRT1

decreases_acetylation of

gene/protein

PPARGC1B

Comment Protein deacetylase SIRT1 (the mammalian Sir2 ortholog) deacetylates a number of nonhistone targets including PGC-1alpha and PGC-1beta, with activation of both cofactors.
Formal Description
Interaction-ID: 4817

gene/protein

SIRT1

increases_activity of

gene/protein

PPARGC1B

Comment SIRT1, located in the cell nucleus, requires NAD(+) as a cofactor and is negatively regulated by either NADH or the deacetylation product nicotinamide.
Formal Description
Interaction-ID: 4818

gene/protein

SIRT1

is localized in

cellular component

nucleus

Comment PGC-1alpha target genes for fatty acid (FA) oxidation are induced in skeletal muscle by SIRT1 and inhibited by GCN5.
Formal Description
Interaction-ID: 4869

gene/protein

SIRT1

increases_activity of

gene/protein

PPARGC1A

in skeletal muscle
Comment SIRT1 has been reported to deacetylate TORC2 leading to its ubiquitin-mediated degradation and inhibition of gluconeogenic gene expression.
Formal Description
Interaction-ID: 4905

gene/protein

SIRT1

decreases_acetylation of

gene/protein

CRTC2

Comment SIRT1 has been reported to deacetylate TORC2 leading to its ubiquitin-mediated degradation and inhibition of gluconeogenic gene expression.
Formal Description
Interaction-ID: 4906

gene/protein

SIRT1

decreases_quantity of

gene/protein

CRTC2

via ubiquitin-mediated degradation of CRTC2
Comment SIRT1 has been reported to deacetylate TORC2 leading to its ubiquitin-mediated degradation and inhibition of gluconeogenic gene expression.
Formal Description
Interaction-ID: 4907

gene/protein

SIRT1

decreases_activity of

process

gluconeogenesis

Comment SIRT1 acts on targets in a signal-specific manner, deacetylating PGC-1alpha only in response to nutrient signaling but not glucagon.
Formal Description
Interaction-ID: 4908

gene/protein

Glucagon

NOT affects_activity of

gene/protein

SIRT1

Comment Increased SIRT1 expression specifically in pancreatic beta-cells, which would be predicted to induce PPAR-alpha signaling through deacetylation and induction of PGC-1alpha, improves glucose tolerance and enhances insulin secretion, in particular first-phase insulin secretion in response to glucose.
Formal Description
Interaction-ID: 4917

gene/protein

SIRT1

increases_activity of

in pancreas, in pancreatic islets
Comment Increased SIRT1 expression specifically in pancreatic beta-cells, which would be predicted to induce PPAR-alpha signaling through deacetylation and induction of PGC-1alpha, improves glucose tolerance and enhances insulin secretion, in particular first-phase insulin secretion in response to glucose.
Formal Description
Interaction-ID: 4918

gene/protein

SIRT1

increases_activity of

in pancreas, in pancreatic islets
Comment The expression of Ucp2 and the prolactin receptor gene (Prlr), both of which significantly influence beta-cell function, were downregulated by SIRT1 overexpression.
Formal Description
Interaction-ID: 4919

gene/protein

SIRT1

decreases_expression of

gene/protein

UCP2

in pancreas, in pancreatic islets
Comment The expression of Ucp2 and the prolactin receptor gene (Prlr), both of which significantly influence beta-cell function, were downregulated by SIRT1 overexpression.
Formal Description
Interaction-ID: 4920

gene/protein

SIRT1

decreases_expression of

gene/protein

PRLR

in pancreas, in pancreatic islets
Drugbank entries Show/Hide entries for PRLR
Comment SIRT1 deacetylates and thus positively regulates LXR.
Formal Description
Interaction-ID: 4951

gene/protein

SIRT1

decreases_acetylation of

gene/protein

NR1H

Comment SIRT1 deacetylates and thus positively regulates LXR.
Formal Description
Interaction-ID: 4952

gene/protein

SIRT1

increases_activity of

gene/protein

NR1H

Comment In mature adipocytes, SIRT1 binds and represses PPAR-gamma in association with mobilization of fat stores during food deprivation.
Formal Description
Interaction-ID: 5076

gene/protein

SIRT1

interacts (colocalizes) with

gene/protein

PPARG

in adipose tissue, in mature adipocytes
Drugbank entries Show/Hide entries for PPARG
Comment In mature adipocytes, SIRT1 binds and represses PPAR-gamma in association with mobilization of fat stores during food deprivation.
Formal Description
Interaction-ID: 5078

gene/protein

SIRT1

decreases_activity of

gene/protein

PPARG

in adipose tissue, in mature adipocytes
Drugbank entries Show/Hide entries for PPARG
Comment In mature adipocytes, SIRT1 binds and represses PPAR-gamma in association with mobilization of fat stores during food deprivation.
Formal Description
Interaction-ID: 5080

gene/protein

SIRT1

increases_activity of

process

fat reserve metabolic process

in adipose tissue, in mature adipocytes; during food deprivation
Comment Small molecular weight molecules, including SRT1460 and SRT1720, that selectively activate SIRT1 and are 1000-fold more potent activators than (and structurally unrelated to) resveratrol have been identified. The therapeutic potential of SIRT1 activators to treat insulin resistance and diabetes has been examined in vivo in models of T2DM. SRT1720 opposes hyperinsulinemia and the impairment in glucose tolerance introduced by high-fat feeding in mice to an extent similar to that achieved with rosiglitazone.
Formal Description
Interaction-ID: 5136

drug/chemical compound

SRT1720

increases_activity of

gene/protein

SIRT1