In:
Diabetes, American Diabetes Association, Vol. 51, No. 7 ( 2002-07-01), p. 2005-2011
Abstract:
The possibility that lipid-induced insulin resistance in human muscle is related to alterations in diacylglycerol (DAG)/protein kinase C (PKC) signaling was investigated in normal volunteers during euglycemic-hyperinsulinemic clamping in which plasma free fatty acid (FFA) levels were increased by a lipid/heparin infusion. In keeping with previous reports, rates of insulin-stimulated glucose disappearance (GRd) were normal after 2 h but were reduced by 43% (from 52.7 ± 8.2 to 30.0 ± 5.3 μmol · kg–1 · min–1, P & lt; 0.05) after 6 h of lipid infusion. No changes in PKC activity or DAG mass were seen in muscle biopsy samples after 2 h of lipid infusion; however, at ∼6 h, PKC activity and DAG mass were increased approximately fourfold, as were the abundance of membrane-associated PKC-βII and -δ. A threefold increase in membrane-associated PKC-βII was also observed at ∼2 h but was not statistically significant (P = 0.058). Ceramide mass was not changed at either time point. To evaluate whether the fatty acid–induced insulin activation of PKC was associated with a change in the IkB kinase (IKK)/nuclear factor (NF)-κB pathway, we determined the abundance in muscle of IκB-α, an inhibitor of NF-κB that is degraded after its phosphorylation by IKK. In parallel with the changes in DAG/PKC, no change in IκB-α mass was observed after 2 h of lipid infusion, but at ∼6 h, IκB-α was diminished by 70%. In summary, the results indicated that the insulin resistance observed in human muscle when plasma FFA levels were elevated during euglycemic-hyperinsulinemic clamping was associated with increases in DAG mass and membrane-associated PKC-βII and -δ and a decrease in IκB-α. Whether acute FFA-induced insulin resistance in human skeletal muscle is caused by the activation of these specific PKC isoforms and the IKK-β/IκB/NFκB pathway remains to be established.
Type of Medium:
Online Resource
ISSN:
0012-1797
,
1939-327X
DOI:
10.2337/diabetes.51.7.2005
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2002
detail.hit.zdb_id:
1501252-9
Permalink