General Information:

Id: 868
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mus musculus
male
SirBACO: SirT1 bacterial artificial chromosome overexpressor
article
Reference: Banks AS et al.(2008) SirT1 gain of function increases energy efficiency and prevents diabetes in mice. Cell Metab. 8: 333-341 [PMID: 18840364]

Interaction Information:

Comment Metabolic characterization of SirBACO mice was carried out on a standard diet. Serum metabolite levels, including insulin and glucose, were normal, as was the response to intraperitoneal glucose or insulin challenge tests. However, an about 30% increase in plasma adiponectin levels was detected.
Formal Description
Interaction-ID: 5146

gene/protein

SIRT1

NOT affects_quantity of

complex/PPI

Insulin

in blood; on standard diet, if SIRT1 is overexpressed
Comment Metabolic characterization of SirBACO mice was carried out on a standard diet. Serum metabolite levels, including insulin and glucose, were normal, as was the response to intraperitoneal glucose or insulin challenge tests. However, an about 30% increase in plasma adiponectin levels was detected.
Formal Description
Interaction-ID: 5148

gene/protein

SIRT1

NOT affects_quantity of

drug/chemical compound

Glucose

in blood; on standard diet, if SIRT1 is overexpressed
Comment Metabolic characterization of SirBACO mice was carried out on a standard diet. Serum metabolite levels, including insulin and glucose, were normal, as was the response to intraperitoneal glucose or insulin challenge tests. However, an about 30% increase in plasma adiponectin levels was detected.
Formal Description
Interaction-ID: 5149

gene/protein

SIRT1

NOT affects_activity of

on standard diet, if SIRT1 is overexpressed
Comment Metabolic characterization of SirBACO mice was carried out on a standard diet. Serum metabolite levels, including insulin and glucose, were normal, as was the response to intraperitoneal glucose or insulin challenge tests. However, an about 30% increase in plasma adiponectin levels was detected.
Formal Description
Interaction-ID: 5181

gene/protein

SIRT1

NOT affects_activity of

on standard diet, if SIRT1 is overexpressed
Comment Metabolic characterization of SirBACO mice was carried out on a standard diet. Serum metabolite levels, including insulin and glucose, were normal, as was the response to intraperitoneal glucose or insulin challenge tests. However, an about 30% increase in plasma adiponectin levels was detected.
Formal Description
Interaction-ID: 5182

gene/protein

SIRT1

increases_quantity of

gene/protein

ADIPOQ

in blood; on standard diet, if SIRT1 is overexpressed
Comment SirBACO mice on a normal diet had decreased resting energy expenditure, but no differences at higher activity levels. Body weight and composition were similar in SirBACO mice and nontransgenic littermates. Food intake decreased by 15% in SirBACO mice, consistent with the preservation of normal body weight, in the face of decreased metabolic rate and activity.
Formal Description
Interaction-ID: 5184

gene/protein

SIRT1

affects_activity of

on standard diet, if SIRT1 is overexpressed
Comment SirBACO mice are protected from insulin-resistant diabetes.
Formal Description
Interaction-ID: 5185

gene/protein

SIRT1

decreases_activity of

disease

Insulin resistance

if SIRT1 is overexpressed
Comment In contrast to the findings in SirBACO mice on a normal diet, there were no differences in metabolic rate, spontaneous locomotor activity, or food intake in SirBACO mice on a high-fat diet or crossed onto db/db compared to littermate controls, thus it seems that SirT1 promotes a state of increased energy efficiency that protects against insulin resistance and hyperglycemia.
Formal Description
Interaction-ID: 5186

gene/protein

SIRT1

NOT affects_activity of

on high-fat diet, if SIRT1 is overexpressed
Comment Plasma insulin levels were lower in high fat-fed SirBACO and SirBACO::db/db mice, consistent with improved insulin sensitivity.
Formal Description
Interaction-ID: 5187

gene/protein

SIRT1

decreases_quantity of

complex/PPI

Insulin

in blood; on high-fat diet, if SIRT1 is overexpressed
Comment Whereas high fat feeding was associated with a modest decrease in plasma adiponectin levels in wild-type mice, in SirBACO mice a 30%-40% rise was observed, suggesting that the ability to prevent hyperglycemia is due to increased adiponectin synthesis/secretion, independent of differences in body fat mass.
Formal Description
Interaction-ID: 5188

gene/protein

SIRT1

increases_quantity of

gene/protein

ADIPOQ

in blood; on high-fat diet, if SIRT1 is overexpressed
Comment In SirBACO mice on high-fat diet no differences were found in resistin, PAI-1, TNF-alpha, or leptin levels.
Formal Description
Interaction-ID: 5189

gene/protein

SIRT1

NOT affects_quantity of

gene/protein

RETN

in blood; on high-fat diet, if SIRT1 is overexpressed
Comment In SirBACO mice on high-fat diet no differences were found in resistin, PAI-1, TNF-alpha, or leptin levels.
Formal Description
Interaction-ID: 5190

gene/protein

SIRT1

NOT affects_quantity of

gene/protein

SERPINE1

in blood; on high-fat diet, if SIRT1 is overexpressed
Drugbank entries Show/Hide entries for SERPINE1
Comment In SirBACO mice on high-fat diet no differences were found in resistin, PAI-1, TNF-alpha, or leptin levels.
Formal Description
Interaction-ID: 5191

gene/protein

SIRT1

NOT affects_quantity of

gene/protein

TNF

in blood; on high-fat diet, if SIRT1 is overexpressed
Drugbank entries Show/Hide entries for TNF
Comment In SirBACO mice on high-fat diet no differences were found in resistin, PAI-1, TNF-alpha, or leptin levels.
Formal Description
Interaction-ID: 5193

gene/protein

SIRT1

NOT affects_quantity of

gene/protein

LEP

in blood; on high-fat diet, if SIRT1 is overexpressed
Comment To identify the source of increased adiponectin levels, adiponectin mRNA was measured in white adipose tissue (WAT) from mice fed either standard or high-fat diets and a similar increase was observed.
Formal Description
Interaction-ID: 5194

gene/protein

SIRT1

increases_expression of

gene/protein

ADIPOQ

in white adipose tissue; on standard diet, on high-fat diet, if SIRT1 is overexpressed
Comment In SirBACO mice plasma adiponectin isoform distribution was unchanged, with increases in both the high and medium molecular weight components. Consistent with the observed hyperadiponectinemia, high fat-fed SirBACO and SirBACO::db/db mice showed elevated phospho-AMPK levels in WAT, liver, and skeletal muscle. Notably, SirT1 appears to prevent the obesity-driven decrease in phospho-AMPK levels.
Formal Description
Interaction-ID: 5197

gene/protein

SIRT1

increases_activity of

complex/PPI

AMPK

in white adipose tissue, in liver, in skeletal muscle; on high-fat diet, if SIRT1 is overexpressed
Comment In high-fat fed SirBACO mice higher mRNA levels of Ppar-alpha and its target genes, Cpt1 and Adipor2, were found in liver.
Formal Description
Interaction-ID: 5199

gene/protein

SIRT1

increases_expression of

gene/protein

PPARA

in liver; on high-fat diet, if SIRT1 is overexpressed
Drugbank entries Show/Hide entries for PPARA
Comment In high-fat fed SirBACO mice higher mRNA levels of Ppar-alpha and its target genes, Cpt1 and Adipor2, were found in liver.
Formal Description
Interaction-ID: 5201

gene/protein

SIRT1

increases_expression of

gene/protein

CPT1A

in liver; on high-fat diet, via increased PPAR-alpha expression, if SIRT1 is overexpressed
Drugbank entries Show/Hide entries for CPT1A
Comment In high-fat fed SirBACO mice higher mRNA levels of Ppar-alpha and its target genes, Cpt1 and Adipor2, were found in liver.
Formal Description
Interaction-ID: 5202

gene/protein

SIRT1

increases_expression of

gene/protein

ADIPOR2

in liver; on high-fat diet, via increased PPAR-alpha expression, if SIRT1 is overexpressed
Comment SirT1 deacetylates FoxO1 at multiple sites, increasing FoxO1 transcriptional activity. Indeed, acetyl-FoxO1 levels were decreased in hepatocytes from SirBACO mice compared to controls, as were acetyl-Pgc1alpha levels in muscle.
Formal Description
Interaction-ID: 5205

gene/protein

SIRT1

decreases_acetylation of

gene/protein

FOXO1

Comment SirT1 deacetylates FoxO1 at multiple sites, increasing FoxO1 transcriptional activity. Indeed, acetyl-FoxO1 levels were decreased in hepatocytes from SirBACO mice compared to controls, as were acetyl-Pgc1alpha levels in muscle.
Formal Description
Interaction-ID: 5207

gene/protein

SIRT1

decreases_acetylation of

gene/protein

FOXO1

in liver; if SIRT1 is overexpressed
Comment SirT1 deacetylates FoxO1 at multiple sites, increasing FoxO1 transcriptional activity. Indeed, acetyl-FoxO1 levels were decreased in hepatocytes from SirBACO mice compared to controls, as were acetyl-Pgc1alpha levels in muscle.
Formal Description
Interaction-ID: 5208

gene/protein

SIRT1

decreases_acetylation of

gene/protein

PPARGC1A

in skeletal muscle; if SIRT1 is overexpressed
Comment SirBACO mice on a normal diet had decreased resting energy expenditure, but no differences at higher activity levels. Body weight and composition were similar in SirBACO mice and nontransgenic littermates. Food intake decreased by 15% in SirBACO mice, consistent with the preservation of normal body weight, in the face of decreased metabolic rate and activity.
Formal Description
Interaction-ID: 13148

gene/protein

SIRT1

NOT affects_activity of

on standard diet, if SIRT1 is overexpressed