General Information:

Id: 1,162 (click here to show other Interactions for entry)
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 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 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 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 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 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 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