General Information:

Id: 1,963 (click here to show other Interactions for entry)
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Rattus norvegicus
male
article
Reference: Koves TR et al.(2008) Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 7: 45-56 [PMID: 18177724]

Interaction Information:

Comment In response to overnight fasting, in serum most lipid-derived acylcarnitines increased, whereas the amino acid intermediates decreased. Consistent with the fasting-induced rise in circulating NEFA, this profile implies a metabolic switch favoring higher rates of beta-oxidation and diminished degradation of amino acids.
Formal Description
Interaction-ID: 15399

environment

fasting

increases_activity of

Comment Under fasting conditions, serum acylcarnitines were similar between the two diet groups. Conversely, serum samples collected in the fed state revealed higher levels of several fatty acid-derived species and reduced levels of C3, C4, and C5 in HF-fed animals compared to SC-fed animals.
Formal Description
Interaction-ID: 15401

environment

high-fat diet

increases_activity of

Comment Consistent with the serum profile, a marked accumulation of fatty acylcarnitine species in muscles from HF-fed rats was observed. Whereas SC-fed rats lowered most muscle fatty acylcarnitines during the transition from the fasted to the fed state, HF-fed animals exhibited little or no change. Thus, during fasted conditions, the import of fatty acids into muscle mitochondria appears to exceed metabolic demand. Feeding relieved the surplus, but only in the SC-fed group, suggesting that mitochondria from obese animals are unable to appropriately adjust fatty acid influx in response to nutritional status.
Formal Description
Interaction-ID: 15402

environment

high-fat diet

increases_activity of

in skeletal muscle
Comment In contrast to skeletal muscle, liver acylcarnitines were not elevated in HF-fed animals compared to SC-fed animals.
Formal Description
Interaction-ID: 15403

environment

high-fat diet

NOT increases_activity of

in liver
Comment In cultured L6 myotubes, lipid-induced insulin resistance was prevented by manipulations that restrict fatty acid uptake into mitochondria. Insulin resistance in L6 myocytes requires beta-oxidation.
Formal Description
Interaction-ID: 15411

increases_activity of

disease

Insulin resistance

in skeletal muscle