CIDeRGeneral Information:
| Id: | 1,913 |
| Diseases: |
Diabetes mellitus, type II
- [OMIM]
Insulin resistance Obesity - [OMIM] |
| Mus musculus | |
| male | |
| article | |
| Reference: | Hosoi T et al.Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes in mice [PMID: 20824098] |
Interaction Information:
| Comment | MyD88-deficiency exacerbates diabetes without affecting body weight or adiposity. |
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Formal Description Interaction-ID: 14673 |
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| Comment | MyD88-deficiency exacerbates diabetes without affecting body weight or adiposity. |
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Formal Description Interaction-ID: 14674 |
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| Comment | As the activation of c-Jun amino-terminal kinase (JNK) in the liver plays a critical role in the development of diabetes, the level of phosphorylated JNK was examined in MyD88-deficient mice. In normal mice fed a high-fat diet an increase in the phosphorylation of JNK was observed, the increase was drastically enhanced in MyD88-deficient mice on the HFD. The result was unexpected because MyD88-deficient mice are resistant to the LPS-induced activation of JNK. |
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Formal Description Interaction-ID: 14675 |
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| Drugbank entries | Show/Hide entries for MAPK8 |
| Comment | The level of mRNA encoding TNF-alpha was elevated in HFD-fed control mice. However, this increase was markedly inhibited in MyD88-deficient mice on the HFD. Thus, TNF-alpha expression is induced via a MyD88-dependent pathway in mice fed a HFD. |
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Formal Description Interaction-ID: 14676 |
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| Drugbank entries | Show/Hide entries for TNF |
| Comment | The level of mRNA encoding TNF-alpha was elevated in HFD-fed control mice. However, this increase was markedly inhibited in MyD88-deficient mice on the HFD. Thus, TNF-alpha expression is induced via a MyD88-dependent pathway in mice fed a HFD. |
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Formal Description Interaction-ID: 14677 |
affects_expression of gene/protein |
| Drugbank entries | Show/Hide entries for TNF |
| Comment | The increase of the cholesterol (total, free and esterified cholesterol) levels was markedly higher in MyD88-deficient mice fed the HFD, compared to normal HFD-fed mice. |
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Formal Description Interaction-ID: 14678 |
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| Drugbank entries | Show/Hide entries for |
| Comment | The increase of the cholesterol (total, free and esterified cholesterol) levels was markedly higher in MyD88-deficient mice fed the HFD, compared to normal HFD-fed mice. |
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Formal Description Interaction-ID: 14679 |
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| Drugbank entries | Show/Hide entries for |
| Comment | Low density lipoprotein receptor (LDLR) was drastically up-regulated in the liver sample of MyD88-deficient mice fed the HFD, suggesting positive feedback regulation against the increased circulating levels of cholesterols to remove them. |
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Formal Description Interaction-ID: 14680 |
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| Drugbank entries | Show/Hide entries for LDLR |
| Comment | The transcriptional level of HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis, was up-regulated in the liver sample of MyD88-deficient mice fed the HFD. |
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Formal Description Interaction-ID: 14681 |
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| Drugbank entries | Show/Hide entries for HMGCR |
| Comment | The diabetic phenotype observed in Myd88-deficient mice was due at least in part to increased apoptosis in the liver possibly mediated via hypercholesterolemia. |
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Formal Description Interaction-ID: 14682 |
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| Comment | The serum concentration of alanine aminotransferase (ALT), a marker of hepatic injury, was significantly elevated in MyD88-deficient mice fed the HFD compared with normal mice. |
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Formal Description Interaction-ID: 14684 |
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| Drugbank entries | Show/Hide entries for GPT |