General Information:

Id: 6,509 (click here to show other Interactions for entry)
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Homo sapiens
article
Reference: Bandyopadhyay GK et al.(2006) Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects Diabetes 55: 2277-2285 [PMID: 16873691]

Interaction Information:

Comment Malonyl-CoA is produced by activated ACC, and insulin is known to activate ACC by mediating its dephosphorylation. In the basal state, 40% of ACC was in the phosphorylated inactive form in the lean subjects. Additionally, in these subjects, insulin stimulation had a marked effect to dephosphorylate and activate ACC. In the insulin-resistant obese and type 2 diabetic subjects, basal ACC levels were already highly activated, and no further effect of insulin was noted. After rosiglitazone treatment, the type 2 diabetic subjects showed restoration of basal phospho-ACC levels toward normal, with a substantial recovery of the insulin effect to dephosphorylate ACC. These results are fully consistent with the role of ACC to convert acetyl-CoA to malonyl-CoA.
Formal Description
Interaction-ID: 61842

drug/chemical compound

Rosiglitazone

decreases_activity of

gene/protein

ACACA

in muscle
Drugbank entries Show/Hide entries for Rosiglitazone or ACACA
Comment In the insulin-resistant groups, the combined activities of AMPK-alpha1 and -alpha2 in the preclamp state were reduced compared with lean control subjects. When the level of phospho-AMPK was normalized to total AMPK protein levels, a similar trend was observed, but the decrease in phosphorylation of AMPK in the insulin-resistant groups was not statistically significant. After 3 months of rosiglitazone treatment in the type 2 diabetic patients, basal levels of AMPK activities were completely normalized, and the inhibitory effect of insulin on AMP kinase activity was largely restored.
Formal Description
Interaction-ID: 61848

drug/chemical compound

Rosiglitazone

affects_activity of

complex/PPI

AMPK

in muscle
Drugbank entries Show/Hide entries for Rosiglitazone
Comment In type 2 diabetic subjects, basal fatty acid oxidation rates were significantly reduced with no significant further effect of insulin. After rosiglitazone treatment, basal fatty acid oxidation rates were partially restored to normal, and the insulin effect to lower fatty acid oxidation was restored.
Formal Description
Interaction-ID: 61856

drug/chemical compound

Rosiglitazone

increases_activity of

in muscle
Drugbank entries Show/Hide entries for Rosiglitazone
Comment Another control point for muscle fatty acid oxidation relates to the ability of muscle cells to take up fatty acids through fatty acid transporters/translocators. Therefore, FAT/ CD36 and FATP4 were measured in muscle homogenates plasma membrane and microsomal fractions obtained in both the basal and insulin-stimulated state. In the lean subjects, insulin had the expected effect to increase translocation of these two proteins from the microsomes to the plasma membrane, but this insulin effect was absent in the untreated type 2 diabetic subjects. Furthermore, basal levels of FAT/CD36 expression were substantially elevated in plasma membrane fractions of the type 2 diabetic subjects, and a modest increase in the FATP4 content was also noted. FATP1 levels were not different between any of the subject groups. After rosiglitazone treatment, basal fatty acid levels of FAT/CD36 and FATP4 remained elevated, but the effect of insulin to induce translocation to the plasma membrane fraction was completely restored. This is consistent with the view that fatty acid uptake is increased in insulin-resistant type 2 diabetic subjects, but that the intracellular fatty acids are preferentially directed toward lipogenesis rather than oxidation.
Formal Description
Interaction-ID: 61878

drug/chemical compound

Rosiglitazone

affects transport of

gene/protein

CD36

to plasma membrane, in muscle
Drugbank entries Show/Hide entries for Rosiglitazone
Comment Another control point for muscle fatty acid oxidation relates to the ability of muscle cells to take up fatty acids through fatty acid transporters/translocators. Therefore, FAT/ CD36 and FATP4 were measured in muscle homogenates plasma membrane and microsomal fractions obtained in both the basal and insulin-stimulated state. In the lean subjects, insulin had the expected effect to increase translocation of these two proteins from the microsomes to the plasma membrane, but this insulin effect was absent in the untreated type 2 diabetic subjects. Furthermore, basal levels of FAT/CD36 expression were substantially elevated in plasma membrane fractions of the type 2 diabetic subjects, and a modest increase in the FATP4 content was also noted. FATP1 levels were not different between any of the subject groups. After rosiglitazone treatment, basal fatty acid levels of FAT/CD36 and FATP4 remained elevated, but the effect of insulin to induce translocation to the plasma membrane fraction was completely restored. This is consistent with the view that fatty acid uptake is increased in insulin-resistant type 2 diabetic subjects, but that the intracellular fatty acids are preferentially directed toward lipogenesis rather than oxidation.
Formal Description
Interaction-ID: 61879

drug/chemical compound

Rosiglitazone

affects transport of

gene/protein

SLC27A4

to plasma membrane, in muscle
Drugbank entries Show/Hide entries for Rosiglitazone