General Information:

Id: 1,162
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mus musculus
LIKK mouse: mouse selectively expressing constitutively active IKK-beta in hepatocytes; LISR mouse: mouse selectively expressing the I-kappa-B-alpha superrepressor in liver
article
Reference: Cai D et al.(2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat. Med. 11: 183-190 [PMID: 15685173]

Interaction Information:

Comment High-fat diet (HFD) increased insulin resistance in C57Bl/6 mice by 2.5-fold, quantified by homeostasis model assessmen-insulin resistance (HOMA-IR), an established measure of insulin sensitivity.
Formal Description
Interaction-ID: 7624

environment

high-fat diet

increases_activity of

disease

Insulin resistance

Comment HFD was accompanied by 1.9- and 1.4-fold increases in hepatic triglyceride (TG) content and serum free fatty acid (FFA) concentrations, respectively, and a twofold increase in hepatic NF-kappaB activity.
Formal Description
Interaction-ID: 7629

environment

high-fat diet

increases_quantity of

drug/chemical compound

Triacylglycerol

in liver
Comment HFD was accompanied by 1.9- and 1.4-fold increases in hepatic triglyceride (TG) content and serum free fatty acid (FFA) concentrations, respectively, and a twofold increase in hepatic NF-kappaB activity.
Formal Description
Interaction-ID: 7630

environment

high-fat diet

increases_quantity of

drug/chemical compound

Fatty acid

in blood
Comment HFD was accompanied by 1.9- and 1.4-fold increases in hepatic triglyceride (TG) content and serum free fatty acid (FFA) concentrations, respectively, and a twofold increase in hepatic NF-kappaB activity.
Formal Description
Interaction-ID: 7647

environment

high-fat diet

increases_activity of

complex/PPI

NF-kappaB complex

in liver
Comment Message levels of NF-kappaB targets were elevated by HFD. mRNAs encoding IL-6, Il-1beta and TNF-alpha were increased by 6.1-, 3.5- and 2.6-fold, respectively. Each of the encoded cytokines has been associated previously with the development of insulin resistance.
Formal Description
Interaction-ID: 7650

environment

high-fat diet

increases_expression of

gene/protein

IL6

Drugbank entries Show/Hide entries for IL6
Comment Message levels of NF-kappaB targets were elevated by HFD. mRNAs encoding IL-6, Il-1beta and TNF-alpha were increased by 6.1-, 3.5- and 2.6-fold, respectively. Each of the encoded cytokines has been associated previously with the development of insulin resistance.
Formal Description
Interaction-ID: 7651

environment

high-fat diet

increases_expression of

gene/protein

TNF

Drugbank entries Show/Hide entries for TNF
Comment Message levels of NF-kappaB targets were elevated by HFD. mRNAs encoding IL-6, Il-1beta and TNF-alpha were increased by 6.1-, 3.5- and 2.6-fold, respectively. Each of the encoded cytokines has been associated previously with the development of insulin resistance.
Formal Description
Interaction-ID: 7653

environment

high-fat diet

increases_expression of

gene/protein

IL1B

Drugbank entries Show/Hide entries for IL1B
Comment On high-fat diet two- to threefold increases were seen in the levels of mRNAs encoding cytokine (TNFR1a and IL-8R) and Toll (TLR-2 and TLR-4) receptors and suppressors of cytokine signaling (SOCS-1, SOCS-2 and SOCS-3). Although the Socs genes are not themselves NF-kappaB targets, their expression is driven by many cytokines, including those that are NF-kappaB targets.
Formal Description
Interaction-ID: 7654

environment

high-fat diet

increases_expression of

gene/protein

TNFRSF1A

Drugbank entries Show/Hide entries for TNFRSF1A
Comment On high-fat diet two- to threefold increases were seen in the levels of mRNAs encoding cytokine (TNFR1a and IL-8R) and Toll (TLR-2 and TLR-4) receptors and suppressors of cytokine signaling (SOCS-1, SOCS-2 and SOCS-3). Although the Socs genes are not themselves NF-kappaB targets, their expression is driven by many cytokines, including those that are NF-kappaB targets.
Formal Description
Interaction-ID: 7668

environment

high-fat diet

increases_expression of

gene/protein

CXCR

Comment On high-fat diet two- to threefold increases were seen in the levels of mRNAs encoding cytokine (TNFR1a and IL-8R) and Toll (TLR-2 and TLR-4) receptors and suppressors of cytokine signaling (SOCS-1, SOCS-2 and SOCS-3). Although the Socs genes are not themselves NF-kappaB targets, their expression is driven by many cytokines, including those that are NF-kappaB targets.
Formal Description
Interaction-ID: 7669

environment

high-fat diet

increases_expression of

gene/protein

TLR2

Drugbank entries Show/Hide entries for TLR2
Comment On high-fat diet two- to threefold increases were seen in the levels of mRNAs encoding cytokine (TNFR1a and IL-8R) and Toll (TLR-2 and TLR-4) receptors and suppressors of cytokine signaling (SOCS-1, SOCS-2 and SOCS-3). Although the Socs genes are not themselves NF-kappaB targets, their expression is driven by many cytokines, including those that are NF-kappaB targets.
Formal Description
Interaction-ID: 7670

environment

high-fat diet

increases_expression of

gene/protein

TLR4

Drugbank entries Show/Hide entries for TLR4
Comment On high-fat diet two- to threefold increases were seen in the levels of mRNAs encoding cytokine (TNFR1a and IL-8R) and Toll (TLR-2 and TLR-4) receptors and suppressors of cytokine signaling (SOCS-1, SOCS-2 and SOCS-3). Although the Socs genes are not themselves NF-kappaB targets, their expression is driven by many cytokines, including those that are NF-kappaB targets.
Formal Description
Interaction-ID: 7671

environment

high-fat diet

increases_expression of

gene/protein

SOCS1

Comment On high-fat diet two- to threefold increases were seen in the levels of mRNAs encoding cytokine (TNFR1a and IL-8R) and Toll (TLR-2 and TLR-4) receptors and suppressors of cytokine signaling (SOCS-1, SOCS-2 and SOCS-3). Although the Socs genes are not themselves NF-kappaB targets, their expression is driven by many cytokines, including those that are NF-kappaB targets.
Formal Description
Interaction-ID: 7672

environment

high-fat diet

increases_expression of

gene/protein

SOCS2

Comment On high-fat diet two- to threefold increases were seen in the levels of mRNAs encoding cytokine (TNFR1a and IL-8R) and Toll (TLR-2 and TLR-4) receptors and suppressors of cytokine signaling (SOCS-1, SOCS-2 and SOCS-3). Although the Socs genes are not themselves NF-kappaB targets, their expression is driven by many cytokines, including those that are NF-kappaB targets.
Formal Description
Interaction-ID: 7674

environment

high-fat diet

increases_expression of

gene/protein

SOCS3

Comment Elevated fasting insulin levels in both male and female LIKK mice, and normal fasting blood glucose and FFA levels, suggested a state of compensated insulin resistance.
Formal Description
Interaction-ID: 7675

gene/protein

IKBKB

increases_activity of

disease

Insulin resistance

in male and female LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment Glucose intolerance and insulin resistance increased in parallel to show a dose-dependent relationship between NF-kappaB activity in liver and the development of systemic insulin resistance.
Formal Description
Interaction-ID: 7677

complex/PPI

NF-kappaB complex

increases_activity of

disease

Insulin resistance

Comment Expression of mRNAs encoding the rate-limiting enzymes in gluconeogenesis, phosphoenolpyruvate carboxykinase and glucose- 6-phosphatase, was appropriately suppressed by feeding in wildtype controls. In contrast, the expression of mRNA encoding glucose-6-phosphatase was elevated in fasting LIKK mice and feeding did not suppress the expression of mRNAs encoding both phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. These findings show that NF-kappaB activation in hepatocytes causes hepatic insulin resistance.
Formal Description
Interaction-ID: 7679

gene/protein

IKBKB

increases_expression of

gene/protein

G6PC

in LIKK mice, after feeding
Drugbank entries Show/Hide entries for IKBKB
Comment Expression of mRNAs encoding the rate-limiting enzymes in gluconeogenesis, phosphoenolpyruvate carboxykinase and glucose- 6-phosphatase, was appropriately suppressed by feeding in wildtype controls. In contrast, the expression of mRNA encoding glucose-6-phosphatase was elevated in fasting LIKK mice and feeding did not suppress the expression of mRNAs encoding both phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. These findings show that NF-kappaB activation in hepatocytes causes hepatic insulin resistance.
Formal Description
Interaction-ID: 7681

gene/protein

IKBKB

increases_expression of

gene/protein

PCK

in LIKK mice, after feeding
Drugbank entries Show/Hide entries for IKBKB
Comment Insulin receptor phosphorylation increased eightfold in wild-type livers after insulin injections. Basal and insulin-stimulated insulin receptor phosphorylation were both decreased in LIKK liver.
Formal Description
Interaction-ID: 7682

gene/protein

IKBKB

decreases_phosphorylation of

complex/PPI

Insulin receptor

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment The patterns for insulin receptor substrate (IRS)-2 phosphorylation were similar, with decreased specific IRS-2 phosphorylation in LIKK liver.
Formal Description
Interaction-ID: 7685

gene/protein

IKBKB

decreases_phosphorylation of

gene/protein

IRS2

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment IRS-1 phosphorylation was blunted in LIKK muscle.
Formal Description
Interaction-ID: 7686

gene/protein

IKBKB

decreases_phosphorylation of

gene/protein

IRS1

in muscle; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB or IRS1
Comment Similar to the findings in HFD, mRNAs encoding IL-1beta and IL-6 were elevated 3.7- and 8.8-fold, respectively, in livers of LIKK mice.
Formal Description
Interaction-ID: 7689

gene/protein

IKBKB

increases_expression of

gene/protein

IL1B

in LIKK mice
Drugbank entries Show/Hide entries for IKBKB or IL1B
Comment Similar to the findings in HFD, mRNAs encoding IL-1beta and IL-6 were elevated 3.7- and 8.8-fold, respectively, in livers of LIKK mice.
Formal Description
Interaction-ID: 7690

gene/protein

IKBKB

increases_expression of

gene/protein

IL6

in LIKK mice
Drugbank entries Show/Hide entries for IKBKB or IL6
Comment In LIKK liver levels of mRNAs encoding related receptors were also increased, including mRNAs encoding IL-1R1, IL-6ST/gp130, IL-8R and TLR-2. The elevated levels of mRNAs encoding SOCS-1, SOCS-2, SOCS-3 and Stat-3 suggested that cytokines including IL-6 produced in LIKK liver might have local actions.
Formal Description
Interaction-ID: 7692

gene/protein

IKBKB

increases_expression of

gene/protein

IL1R1

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB or IL1R1
Comment In LIKK liver levels of mRNAs encoding related receptors were also increased, including mRNAs encoding IL-1R1, IL-6ST/gp130, IL-8R and TLR-2. The elevated levels of mRNAs encoding SOCS-1, SOCS-2, SOCS-3 and Stat-3 suggested that cytokines including IL-6 produced in LIKK liver might have local actions.
Formal Description
Interaction-ID: 7694

gene/protein

IKBKB

increases_expression of

gene/protein

IL6ST

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment In LIKK liver levels of mRNAs encoding related receptors were also increased, including mRNAs encoding IL-1R1, IL-6ST/gp130, IL-8R and TLR-2. The elevated levels of mRNAs encoding SOCS-1, SOCS-2, SOCS-3 and Stat-3 suggested that cytokines including IL-6 produced in LIKK liver might have local actions.
Formal Description
Interaction-ID: 7696

gene/protein

IKBKB

increases_expression of

gene/protein

CXCR

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment In LIKK liver levels of mRNAs encoding related receptors were also increased, including mRNAs encoding IL-1R1, IL-6ST/gp130, IL-8R and TLR-2. The elevated levels of mRNAs encoding SOCS-1, SOCS-2, SOCS-3 and Stat-3 suggested that cytokines including IL-6 produced in LIKK liver might have local actions.
Formal Description
Interaction-ID: 7697

gene/protein

IKBKB

increases_expression of

gene/protein

TLR2

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB or TLR2
Comment In LIKK liver levels of mRNAs encoding related receptors were also increased, including mRNAs encoding IL-1R1, IL-6ST/gp130, IL-8R and TLR-2. The elevated levels of mRNAs encoding SOCS-1, SOCS-2, SOCS-3 and Stat-3 suggested that cytokines including IL-6 produced in LIKK liver might have local actions.
Formal Description
Interaction-ID: 7698

gene/protein

IKBKB

increases_expression of

gene/protein

SOCS1

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment In LIKK liver levels of mRNAs encoding related receptors were also increased, including mRNAs encoding IL-1R1, IL-6ST/gp130, IL-8R and TLR-2. The elevated levels of mRNAs encoding SOCS-1, SOCS-2, SOCS-3 and Stat-3 suggested that cytokines including IL-6 produced in LIKK liver might have local actions.
Formal Description
Interaction-ID: 7699

gene/protein

IKBKB

increases_expression of

gene/protein

SOCS2

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment In LIKK liver levels of mRNAs encoding related receptors were also increased, including mRNAs encoding IL-1R1, IL-6ST/gp130, IL-8R and TLR-2. The elevated levels of mRNAs encoding SOCS-1, SOCS-2, SOCS-3 and Stat-3 suggested that cytokines including IL-6 produced in LIKK liver might have local actions.
Formal Description
Interaction-ID: 7700

gene/protein

IKBKB

increases_expression of

gene/protein

SOCS3

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment In LIKK liver levels of mRNAs encoding related receptors were also increased, including mRNAs encoding IL-1R1, IL-6ST/gp130, IL-8R and TLR-2. The elevated levels of mRNAs encoding SOCS-1, SOCS-2, SOCS-3 and Stat-3 suggested that cytokines including IL-6 produced in LIKK liver might have local actions.
Formal Description
Interaction-ID: 7701

gene/protein

IKBKB

increases_expression of

gene/protein

STAT3

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment Stat-3 phosphorylation was elevated by 2.4-fold in LIKK liver.
Formal Description
Interaction-ID: 7702

gene/protein

IKBKB

increases_phosphorylation of

gene/protein

STAT3

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment Socs1, Socs2, Socs3 and Stat3 mRNA levels were also elevated in LIKK muscle, suggesting that IKK-beta-NF-kappaB activation in liver affected signaling in muscle.
Formal Description
Interaction-ID: 7704

gene/protein

IKBKB

increases_expression of

gene/protein

SOCS1

in muscle; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment Socs1, Socs2, Socs3 and Stat3 mRNA levels were also elevated in LIKK muscle, suggesting that IKK-beta-NF-kappaB activation in liver affected signaling in muscle.
Formal Description
Interaction-ID: 7705

gene/protein

IKBKB

increases_expression of

gene/protein

SOCS2

in muscle; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment Socs1, Socs2, Socs3 and Stat3 mRNA levels were also elevated in LIKK muscle, suggesting that IKK-beta-NF-kappaB activation in liver affected signaling in muscle.
Formal Description
Interaction-ID: 7706

gene/protein

IKBKB

increases_expression of

gene/protein

SOCS3

in muscle; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment Socs1, Socs2, Socs3 and Stat3 mRNA levels were also elevated in LIKK muscle, suggesting that IKK-beta-NF-kappaB activation in liver affected signaling in muscle.
Formal Description
Interaction-ID: 7707

gene/protein

IKBKB

increases_expression of

gene/protein

STAT3

in muscle; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment Neither NF-kappaB activity nor target message levels were elevated in LIKK muscle, suggesting that a liver-derived cytokine, possibly IL-6, mediated. insulin resistance in muscle.
Formal Description
Interaction-ID: 7708

gene/protein

IKBKB

NOT affects_activity of

complex/PPI

NF-kappaB complex

in muscle; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment A state of chronic, subacute 'inflammation' has been simulated by low-level activation of NF-kappaB in the liver of transgenic mice, designated LIKK, by selectively expressing constitutively active IKK-b in hepatocytes. These mice exhibit a type 2 diabetes phenotype, characterized by hyperglycemia, profound hepatic insulin resistance, and moderate systemic insulin resistance, including effects in muscle.
Formal Description
Interaction-ID: 7710

gene/protein

IKBKB

increases_activity of

complex/PPI

NF-kappaB complex

in liver; in LIKK mice, via selective expression of constitutively active IKK-b in hepatocytes
Drugbank entries Show/Hide entries for IKBKB
Comment A state of chronic, subacute 'inflammation' has been simulated by low-level activation of NF-kappaB in the liver of transgenic mice, designated LIKK, by selectively expressing constitutively active IKK-b in hepatocytes. These mice exhibit a type 2 diabetes phenotype, characterized by hyperglycemia, profound hepatic insulin resistance, and moderate systemic insulin resistance, including effects in muscle.
Formal Description
Interaction-ID: 7711

gene/protein

IKBKB

increases_activity of

in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment A state of chronic, subacute 'inflammation' has been simulated by low-level activation of NF-kappaB in the liver of transgenic mice, designated LIKK, by selectively expressing constitutively active IKK-b in hepatocytes. These mice exhibit a type 2 diabetes phenotype, characterized by hyperglycemia, profound hepatic insulin resistance, and moderate systemic insulin resistance, including effects in muscle.
Formal Description
Interaction-ID: 7712

gene/protein

IKBKB

increases_activity of

phenotype

hyperglycemia

in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment Those messages that were elevated in LIKK muscle, including Socs1, Socs2, Socs3 and Stat3, were reduced by IL-6 neutralization. These findings strongly support a role for IL-6 in the development of insulin resistance in LIKK mice.
Formal Description
Interaction-ID: 7713

gene/protein

IL6

affects_expression of

gene/protein

SOCS1

in muscle; in LIKK mice
Drugbank entries Show/Hide entries for IL6
Comment Salicylate treatment reduced NF-kappaB activity in liver by 32% in LIKK mice and 20% in wild-type mice. In contrast, NF-kappaB activity was indistinguishable in muscle of LIKK and wild-type mice, with or without salicylate treatment.
Formal Description
Interaction-ID: 7714

drug/chemical compound

Sodium salicylate

decreases_activity of

complex/PPI

NF-kappaB complex

in liver; in wild-type mice, in LIKK mouse
Comment Salicylate treatment reduced NF-kappaB activity in liver by 32% in LIKK mice and 20% in wild-type mice. In contrast, NF-kappaB activity was indistinguishable in muscle of LIKK and wild-type mice, with or without salicylate treatment.
Formal Description
Interaction-ID: 7715

drug/chemical compound

Sodium salicylate

NOT affects_activity of

complex/PPI

NF-kappaB complex

in muscle; in wild-type mice, in LIKK mouse
Comment Expression of mRNAs encoding IL-6 and IL-1beta, the cytokines most induced in HFD and LIKK models, was reduced in salicylate-treated animals by more than 50%. Expression patterns for other genes that were coordinately upregulated by HFD or NF-kappaB activation (LIKK) were concordantly downregulated by salicylate, including genes encoding receptors (IL-8R and TLR-2) and signaling proteins (SOCS-1, SOCS-2 and SOCS-3). These findings indicate that salicylate improves systemic insulin sensitivity in LIKK mice through IKK-beta-NF-kappaB inhibition in liver but not in muscle.
Formal Description
Interaction-ID: 7716

drug/chemical compound

Sodium salicylate

decreases_expression of

gene/protein

IL6

in liver
Drugbank entries Show/Hide entries for IL6
Comment Expression of mRNAs encoding IL-6 and IL-1beta, the cytokines most induced in HFD and LIKK models, was reduced in salicylate-treated animals by more than 50%. Expression patterns for other genes that were coordinately upregulated by HFD or NF-kappaB activation (LIKK) were concordantly downregulated by salicylate, including genes encoding receptors (IL-8R and TLR-2) and signaling proteins (SOCS-1, SOCS-2 and SOCS-3). These findings indicate that salicylate improves systemic insulin sensitivity in LIKK mice through IKK-beta-NF-kappaB inhibition in liver but not in muscle.
Formal Description
Interaction-ID: 7717

drug/chemical compound

Sodium salicylate

decreases_expression of

gene/protein

IL1B

in liver
Drugbank entries Show/Hide entries for IL1B
Comment Expression of mRNAs encoding IL-6 and IL-1beta, the cytokines most induced in HFD and LIKK models, was reduced in salicylate-treated animals by more than 50%. Expression patterns for other genes that were coordinately upregulated by HFD or NF-kappaB activation (LIKK) were concordantly downregulated by salicylate, including genes encoding receptors (IL-8R and TLR-2) and signaling proteins (SOCS-1, SOCS-2 and SOCS-3). These findings indicate that salicylate improves systemic insulin sensitivity in LIKK mice through IKK-beta-NF-kappaB inhibition in liver but not in muscle.
Formal Description
Interaction-ID: 7718

drug/chemical compound

Sodium salicylate

decreases_expression of

gene/protein

CXCR

in liver
Comment Expression of mRNAs encoding IL-6 and IL-1beta, the cytokines most induced in HFD and LIKK models, was reduced in salicylate-treated animals by more than 50%. Expression patterns for other genes that were coordinately upregulated by HFD or NF-kappaB activation (LIKK) were concordantly downregulated by salicylate, including genes encoding receptors (IL-8R and TLR-2) and signaling proteins (SOCS-1, SOCS-2 and SOCS-3). These findings indicate that salicylate improves systemic insulin sensitivity in LIKK mice through IKK-beta-NF-kappaB inhibition in liver but not in muscle.
Formal Description
Interaction-ID: 7719

drug/chemical compound

Sodium salicylate

decreases_expression of

gene/protein

TLR2

in liver
Drugbank entries Show/Hide entries for TLR2
Comment Expression of mRNAs encoding IL-6 and IL-1beta, the cytokines most induced in HFD and LIKK models, was reduced in salicylate-treated animals by more than 50%. Expression patterns for other genes that were coordinately upregulated by HFD or NF-kappaB activation (LIKK) were concordantly downregulated by salicylate, including genes encoding receptors (IL-8R and TLR-2) and signaling proteins (SOCS-1, SOCS-2 and SOCS-3). These findings indicate that salicylate improves systemic insulin sensitivity in LIKK mice through IKK-beta-NF-kappaB inhibition in liver but not in muscle.
Formal Description
Interaction-ID: 7720

drug/chemical compound

Sodium salicylate

decreases_expression of

gene/protein

SOCS1

in liver
Comment Expression of mRNAs encoding IL-6 and IL-1beta, the cytokines most induced in HFD and LIKK models, was reduced in salicylate-treated animals by more than 50%. Expression patterns for other genes that were coordinately upregulated by HFD or NF-kappaB activation (LIKK) were concordantly downregulated by salicylate, including genes encoding receptors (IL-8R and TLR-2) and signaling proteins (SOCS-1, SOCS-2 and SOCS-3). These findings indicate that salicylate improves systemic insulin sensitivity in LIKK mice through IKK-beta-NF-kappaB inhibition in liver but not in muscle.
Formal Description
Interaction-ID: 7721

drug/chemical compound

Sodium salicylate

decreases_expression of

gene/protein

SOCS2

in liver
Comment Expression of mRNAs encoding IL-6 and IL-1beta, the cytokines most induced in HFD and LIKK models, was reduced in salicylate-treated animals by more than 50%. Expression patterns for other genes that were coordinately upregulated by HFD or NF-kappaB activation (LIKK) were concordantly downregulated by salicylate, including genes encoding receptors (IL-8R and TLR-2) and signaling proteins (SOCS-1, SOCS-2 and SOCS-3). These findings indicate that salicylate improves systemic insulin sensitivity in LIKK mice through IKK-beta-NF-kappaB inhibition in liver but not in muscle.
Formal Description
Interaction-ID: 7722

drug/chemical compound

Sodium salicylate

decreases_expression of

gene/protein

SOCS3

in liver
Comment Using similar transgenic strategies NF-kappaB in mice was inhibited through expression of dominant inhibitory I-kappaB-alpha (S32A,S36A). Mice that selectively express the I-kappaB-alpha superrepressor in liver and are designated LISR mice. These mice are viable and have normal appearance, body weight, food intake and liver histology.
Formal Description
Interaction-ID: 7723

gene/protein

NFKBIA

affects_activity of

complex/PPI

NF-kappaB complex

in liver
Comment Consistent again with a potential role for IL-6 in the development of obesity- and diet-induced insulin resistance, NF-kappaB inhibition in LISR mice was accompanied by a substantial 64% decrease in Il6 mRNA expression.
Formal Description
Interaction-ID: 7725

gene/protein

NFKBIA

affects_expression of

gene/protein

IL6

in LISR mice
Drugbank entries Show/Hide entries for IL6
Comment mRNA levels of Cd68 and Emr1 (also known as F4/80) were upregulated 1.8-fold in LIKK versus wild-type liver. Without an apparent change in the number of cells, these findings are more consistent with the activation of resident Kupffer cells than recruitment of additional macrophages.
Formal Description
Interaction-ID: 7727

gene/protein

IKBKB

increases_expression of

gene/protein

CD68

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment mRNA levels of Cd68 and Emr1 (also known as F4/80) were upregulated 1.8-fold in LIKK versus wild-type liver. Without an apparent change in the number of cells, these findings are more consistent with the activation of resident Kupffer cells than recruitment of additional macrophages.
Formal Description
Interaction-ID: 7728

gene/protein

IKBKB

increases_expression of

gene/protein

ADGRE1

in liver; in LIKK mice
Drugbank entries Show/Hide entries for IKBKB
Comment The expression of Cd68 and Emr1 were also increased greater than twofold by HFD, and both were decreased by hepatocellular inhibition of NF-kappaB in LISR mice. This is an important result, as it shows that the process initiated by HFD in liver requires parenchymal NF-kappaB activation. Hepatocyte-specific inhibition of NF-kappaB is both necessary and sufficient to concomitantly attenuate insulin resistance and the activation of both widely expressed inflammatory genes and macrophage-specific markers.
Formal Description
Interaction-ID: 7729

environment

high-fat diet

increases_expression of

gene/protein

CD68

in liver
Comment The expression of Cd68 and Emr1 were also increased greater than twofold by HFD, and both were decreased by hepatocellular inhibition of NF-kappaB in LISR mice. This is an important result, as it shows that the process initiated by HFD in liver requires parenchymal NF-kappaB activation. Hepatocyte-specific inhibition of NF-kappaB is both necessary and sufficient to concomitantly attenuate insulin resistance and the activation of both widely expressed inflammatory genes and macrophage-specific markers.
Formal Description
Interaction-ID: 7731

environment

high-fat diet

increases_expression of

gene/protein

ADGRE1

in liver
Comment The expression of Cd68 and Emr1 were also increased greater than twofold by HFD, and both were decreased by hepatocellular inhibition of NF-kappaB in LISR mice. This is an important result, as it shows that the process initiated by HFD in liver requires parenchymal NF-kappaB activation. Hepatocyte-specific inhibition of NF-kappaB is both necessary and sufficient to concomitantly attenuate insulin resistance and the activation of both widely expressed inflammatory genes and macrophage-specific markers.
Formal Description
Interaction-ID: 7732

gene/protein

NFKBIA

affects_expression of

gene/protein

CD68

in liver; in LISR mice
Comment The expression of Cd68 and Emr1 were also increased greater than twofold by HFD, and both were decreased by hepatocellular inhibition of NF-kappaB in LISR mice. This is an important result, as it shows that the process initiated by HFD in liver requires parenchymal NF-kappaB activation. Hepatocyte-specific inhibition of NF-kappaB is both necessary and sufficient to concomitantly attenuate insulin resistance and the activation of both widely expressed inflammatory genes and macrophage-specific markers.
Formal Description
Interaction-ID: 7734

gene/protein

NFKBIA

affects_expression of

gene/protein

ADGRE1

in liver; in LISR mice
Comment Elevated fasting insulin levels in both male and female LIKK mice, and normal fasting blood glucose and FFA levels, suggested a state of compensated insulin resistance.
Formal Description
Interaction-ID: 13254

gene/protein

IKBKB

increases_activity of

in blood; in male and female LIKK mice, after fasting
Drugbank entries Show/Hide entries for IKBKB
Comment Elevated fasting insulin levels in both male and female LIKK mice, and normal fasting blood glucose and FFA levels, suggested a state of compensated insulin resistance.
Formal Description
Interaction-ID: 13255

gene/protein

IKBKB

NOT affects_quantity of

drug/chemical compound

Glucose

in blood; in male and female LIKK mice, after fasting
Drugbank entries Show/Hide entries for IKBKB
Comment Elevated fasting insulin levels in both male and female LIKK mice, and normal fasting blood glucose and FFA levels, suggested a state of compensated insulin resistance.
Formal Description
Interaction-ID: 13256

gene/protein

IKBKB

NOT affects_quantity of

drug/chemical compound

Fatty acid

in blood; in male and female LIKK mice, after fasting
Drugbank entries Show/Hide entries for IKBKB
Comment Those messages that were elevated in LIKK muscle, including Socs1, Socs2, Socs3 and Stat3, were reduced by IL-6 neutralization. These findings strongly support a role for IL-6 in the development of insulin resistance in LIKK mice.
Formal Description
Interaction-ID: 13324

gene/protein

IL6

affects_expression of

gene/protein

SOCS2

in muscle; in LIKK mice
Drugbank entries Show/Hide entries for IL6
Comment Those messages that were elevated in LIKK muscle, including Socs1, Socs2, Socs3 and Stat3, were reduced by IL-6 neutralization. These findings strongly support a role for IL-6 in the development of insulin resistance in LIKK mice.
Formal Description
Interaction-ID: 13327

gene/protein

IL6

affects_expression of

gene/protein

SOCS3

in muscle; in LIKK mice
Drugbank entries Show/Hide entries for IL6
Comment Those messages that were elevated in LIKK muscle, including Socs1, Socs2, Socs3 and Stat3, were reduced by IL-6 neutralization. These findings strongly support a role for IL-6 in the development of insulin resistance in LIKK mice.
Formal Description
Interaction-ID: 13331

gene/protein

IL6

affects_expression of

gene/protein

STAT3

in muscle; in LIKK mice
Drugbank entries Show/Hide entries for IL6