Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5900565 | Diabetes Research and Clinical Practice | 2007 | 8 Pages |
Abstract
Chronic hyperinsulinemia is both a marker and a cause for insulin resistance. This study analyzes the effect of long-term exposure to high insulin levels on insulin-insulin receptor metabolism in human myoblasts. Cells were grown in the presence of low (107Â pM, SkMC-L) or high (1430Â pM, SkMC-H) insulin concentrations. Insulin receptor (IR) phosphorylation, IR internalization, dissociation and recycling, as well as insulin degradation have been investigated. Basal IR phosphorylation was higher in SkMC-H than in SkMC-L (PÂ <Â 0.01) but after acute insulin stimulation (10Â nM insulin for 10Â min), IR phosphorylation increased (PÂ <Â 0.01) in SkMC-L, but not in SkMC-H. Chronic hyperinsulinism significantly decreased insulin-IR complex internalization (PÂ <Â 0.01). Nevertheless the t1/2 value of receptor internalization was similar in both cells. Intracellular dissociation of insulin-IR complex was slightly but significantly lower in SkMC-H than in SkMC-L. Finally, SkMC-H showed a complete, but significantly delayed recycling of IR to plasma membrane (t1/2Â =Â 20Â min versus SkMC-L t1/2Â =Â 7Â min). The time course of intracellular degradation measured by HPLC, showed whenever studied, significantly (PÂ <Â 0.01) higher levels of intracellular intact insulin in cells exposed to high insulin concentrations. Nevertheless, the patterns of insulin degradation were over-imposable between SkMC-H and SkMC-L. In summary, continuous exposure of cultured myoblasts to high insulin levels induces subtle derangements of intracellular receptor trafficking and insulin degradation. These alterations may contribute to the insulin resistance of hyperinsulinemic states such as obesity and Type 2 Diabetes.
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Authors
Anna Bertacca, Annamaria Ciccarone, Paolo Cecchetti, Barbara Vianello, Incoronata Laurenza, Stefano Del Prato, Luca Benzi,