General Information:

Id: 906
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Rattus norvegicus
male
SirT1 ASO: knockdown of SirT1 expression in liver and adipose tissue, diabetic via initial streptozotocin injection and 4 weeks of fructose- and high-fat-feeding
article
Reference: Erion DM et al.(2009) SirT1 knockdown in liver decreases basal hepatic glucose production and increases hepatic insulin responsiveness in diabetic rats. Proc. Natl. Acad. Sci. U.S.A. 106 [PMID: 19549853]

Interaction Information:

Comment SirT1 ASO decreased SirT1 mRNA expression by 77% in liver, and the drop in mRNA corresponded with a 68% decrease in SirT1 protein. Additionally, SirT1 ASO decreased SirT1 mRNA 91% in the adipocyte. In addition, no difference was found in SirT1 mRNA in muscle and a tendency of decreased SirT1 mRNA in brown adipose tissue (BAT).
Formal Description
Interaction-ID: 5402

organism model

SirT1 ASO rat

decreases_expression of

gene/protein

SIRT1

in liver, in white adipose tissue, in brown adipose tissue
Comment SirT1 ASO decreased SirT1 mRNA expression by 77% in liver, and the drop in mRNA corresponded with a 68% decrease in SirT1 protein. Additionally, SirT1 ASO decreased SirT1 mRNA 91% in the adipocyte. In addition, no difference was found in SirT1 mRNA in muscle and a tendency of decreased SirT1 mRNA in brown adipose tissue (BAT).
Formal Description
Interaction-ID: 5426

organism model

SirT1 ASO rat

NOT decreases_expression of

gene/protein

SIRT1

in muscle
Comment Additionally, the transcription of SirT1 in the hypothalamus was measured as a possible explanation for the decreased food intake and no differences in mRNA were found on the normal chow diet.
Formal Description
Interaction-ID: 5427

organism model

SirT1 ASO rat

NOT decreases_expression of

gene/protein

SIRT1

in hypothalamus
Comment SirT1 ASO decreased epididymal white adipose tissue, plasma free fatty acids, leptin, and adiponectin concentrations.
Formal Description
Interaction-ID: 5428

gene/protein

SIRT1

affects_quantity of

drug/chemical compound

Fatty acid

in blood; if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment SirT1 ASO decreased epididymal white adipose tissue, plasma free fatty acids, leptin, and adiponectin concentrations.
Formal Description
Interaction-ID: 5433

gene/protein

SIRT1

affects_quantity of

gene/protein

LEP

in blood; if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment SirT1 ASO decreased epididymal white adipose tissue, plasma free fatty acids, leptin, and adiponectin concentrations.
Formal Description
Interaction-ID: 5436

gene/protein

SIRT1

affects_quantity of

gene/protein

ADIPOQ

in blood; if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment The decreased epididymal white adipose tissue mass in SirT1 ASO could be attributed to a 77% and 72% reduction in peroxisome proliferator-activated receptor gamma (PPAR-gamma) and PPAR-gamma2 transcription respectively.
Formal Description
Interaction-ID: 5438

gene/protein

SIRT1

affects_expression of

gene/protein

PPARG

in epididymal white adipose tissue; both splice variants PPAR-gamma1 and PPAR-gamma2, if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Drugbank entries Show/Hide entries for PPARG
Comment In SirT1 ASO CCAAT/enhancer binding protein alpha (C/EBPalpha) was reduced by 74% in adipose tissue.
Formal Description
Interaction-ID: 5443

gene/protein

SIRT1

affects_quantity of

gene/protein

CEBPA

in adipose tissue; if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment SirT1 ASO treatment did not affect plasma triglycerides or liver triglyceride content.
Formal Description
Interaction-ID: 5445

gene/protein

SIRT1

NOT affects_quantity of

drug/chemical compound

Triacylglycerol

in blood, in liver; if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment Plasma beta-hydroxybutyrate concentrations were decreased 28% in the SirT1 ASO group.
Formal Description
Interaction-ID: 5446

gene/protein

SIRT1

affects_quantity of

drug/chemical compound

(R)-3-Hydroxybutanoate

in blood; if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment SirT1 ASO reduced total plasma cholesterol 29%, which could be attributed to a 33% reduction in HDL cholesterol. Cyp7A1 is a target of LXRalpha, so it is unclear why Cyp7A1 is up-regulated in the SirT1 ASO group. However, this result could explain why SirT1 ASO reduces plasma cholesterol in this rodent model of T2DM.
Formal Description
Interaction-ID: 5449

gene/protein

SIRT1

affects_quantity of

drug/chemical compound

Cholesterol

in blood; if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Drugbank entries Show/Hide entries for
Comment SirT1 ASO down-regulated liver X receptor alpha (LXRalpha) transcription, an important factor in cholesterol transport and metabolism. Accordingly, the LXRalpha transcriptional target HDL uptake receptor (SR-B1) was also down-regulated.
Formal Description
Interaction-ID: 5452

gene/protein

SIRT1

affects_expression of

gene/protein

NR1H3

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Drugbank entries Show/Hide entries for NR1H3
Comment SirT1 ASO down-regulated liver X receptor alpha (LXRalpha) transcription, an important factor in cholesterol transport and metabolism. Accordingly, the LXRalpha transcriptional target HDL uptake receptor (SR-B1) was also down-regulated.
Formal Description
Interaction-ID: 5454

gene/protein

SIRT1

affects_expression of

gene/protein

SCARB1

if SIRT1 is knocked down in liver and white adipose tissue of diabetic rats
Drugbank entries Show/Hide entries for SCARB1
Comment SirT1 ASO down-regulated liver X receptor alpha (LXRalpha) transcription, an important factor in cholesterol transport and metabolism. Accordingly, the LXRalpha transcriptional target HDL uptake receptor (SR-B1) was also down-regulated.
Formal Description
Interaction-ID: 5456

gene/protein

NR1H3

increases_expression of

gene/protein

SCARB1

Drugbank entries Show/Hide entries for NR1H3 or SCARB1
Comment In contrast to previous reports, Cyp7A1 transcription was upregulated with SirT1 ASO, indicating greater bile acid synthesis.
Formal Description
Interaction-ID: 5457

gene/protein

SIRT1

affects_expression of

gene/protein

CYP7A1

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment In contrast to previous reports, Cyp7A1 transcription was upregulated with SirT1 ASO, indicating greater bile acid synthesis.
Formal Description
Interaction-ID: 5458

gene/protein

SIRT1

affects_activity of

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment The low-density lipoprotein (LDL) receptor showed a tendency of increased transcription, and ATP binding cassette G8 (ABCG8), sterol response element-binding protein (SREBP-2), and HMG-CoA reductase were unchanged in the SirT1 ASO group.
Formal Description
Interaction-ID: 5460

gene/protein

SIRT1

affects_expression of

gene/protein

LDLR

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Drugbank entries Show/Hide entries for LDLR
Comment The low-density lipoprotein (LDL) receptor showed a tendency of increased transcription, and ATP binding cassette G8 (ABCG8), sterol response element-binding protein (SREBP-2), and HMG-CoA reductase were unchanged in the SirT1 ASO group.
Formal Description
Interaction-ID: 5462

gene/protein

SIRT1

NOT affects_expression of

gene/protein

ABCG8

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment The low-density lipoprotein (LDL) receptor showed a tendency of increased transcription, and ATP binding cassette G8 (ABCG8), sterol response element-binding protein (SREBP-2), and HMG-CoA reductase were unchanged in the SirT1 ASO group.
Formal Description
Interaction-ID: 5463

gene/protein

SIRT1

NOT affects_expression of

gene/protein

SREBF2

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment The low-density lipoprotein (LDL) receptor showed a tendency of increased transcription, and ATP binding cassette G8 (ABCG8), sterol response element-binding protein (SREBP-2), and HMG-CoA reductase were unchanged in the SirT1 ASO group.
Formal Description
Interaction-ID: 5465

gene/protein

SIRT1

NOT affects_expression of

gene/protein

HMGCR

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Drugbank entries Show/Hide entries for HMGCR
Comment SirT1 ASO increases hepatic insulin sensitivity.
Formal Description
Interaction-ID: 5469

gene/protein

SIRT1

affects_activity of

in liver; if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment SirT1 ASO increased STAT3 acetylation more than two-fold over control ASO-treated rats and STAT3 phosphorylation (Y705) more than three-fold compared with control ASO-treated rats.
Formal Description
Interaction-ID: 5472

gene/protein

SIRT1

affects_acetylation of

gene/protein

STAT3

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment SirT1 ASO increased STAT3 acetylation more than two-fold over control ASO-treated rats and STAT3 phosphorylation (Y705) more than three-fold compared with control ASO-treated rats.
Formal Description
Interaction-ID: 5475

gene/protein

SIRT1

affects_phosphorylation of

gene/protein

STAT3

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment In addition to STAT3, SirT1 ASO increased acetylation 51% and 45% in FOXO1 and PGC-1alpha, respectively.
Formal Description
Interaction-ID: 5478

gene/protein

SIRT1

affects_acetylation of

gene/protein

FOXO1

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment In addition to STAT3, SirT1 ASO increased acetylation 51% and 45% in FOXO1 and PGC-1alpha, respectively.
Formal Description
Interaction-ID: 5480

gene/protein

SIRT1

affects_acetylation of

gene/protein

PPARGC1A

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment The increased acetylation of these transcription factors was associated with 25%, 51%, and 49% decreases in phosphoenolpyruvate carboxylase kinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase) transcription, respectively. Western blot analysis also revealed a corresponding drop in PEPCK protein.
Formal Description
Interaction-ID: 5481

gene/protein

SIRT1

affects_expression of

gene/protein

PCK1

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Drugbank entries Show/Hide entries for PCK1
Comment The increased acetylation of these transcription factors was associated with 25%, 51%, and 49% decreases in phosphoenolpyruvate carboxylase kinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase) transcription, respectively. Western blot analysis also revealed a corresponding drop in PEPCK protein.
Formal Description
Interaction-ID: 5482

gene/protein

SIRT1

affects_expression of

gene/protein

FBP1

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Drugbank entries Show/Hide entries for FBP1
Comment The increased acetylation of these transcription factors was associated with 25%, 51%, and 49% decreases in phosphoenolpyruvate carboxylase kinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase) transcription, respectively. Western blot analysis also revealed a corresponding drop in PEPCK protein.
Formal Description
Interaction-ID: 5484

gene/protein

SIRT1

affects_expression of

gene/protein

G6PC

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats
Comment SirT1 ASO decreases transcription of key gluconeogenic enzymes. The decreased gluconeogenetic gene expression from SirT1 knockdown differs from other reports, possibly because of the length of fasting.
Formal Description
Interaction-ID: 5486

gene/protein

SIRT1

affects_activity of

process

gluconeogenesis

if SIRT1 is knocked down in liver and adipose tissue of diabetic rats