The effect of insulin and exercise on c-Cbl protein abundance and phosphorylation in insulin-resistant skeletal muscle in lean and obese Zucker rats.
journal contributionposted on 2004-03-01, 00:00 authored by Glenn WadleyGlenn Wadley, Clinton BruceClinton Bruce, Nicky Konstantopoulos, J Macauley, Kirsten HowlettKirsten Howlett, J Hawley, David Cameron-Smith
Aims/hypothesis: Recruitment of the protein c-Cbl to the insulin receptor (IR) and its tyrosine phosphorylation via a pathway that is independent from phosphatidylinositol 3prime-kinase is necessary for insulin-stimulated GLUT4 translocation in 3T3-L1 adipocytes. The activation of this pathway by insulin or exercise has yet to be reported in skeletal muscle. Methods: Lean and obese Zucker rats were randomly assigned to one of three treatment groups: (i) control, (ii) insulin-stimulated or (iii) acute, exhaustive exercise. Hind limb skeletal muscle was removed and the phosphorylation state of IR, Akt and c-Cbl measured. Results: Insulin receptor phosphorylation was increased 12-fold after insulin stimulation (p<0.0001) in lean rats and threefold in obese rats. Acute exercise had no effect on IR tyrosine phosphorylation. Similar results were found for serine phosphorylation of Akt. Exercise did not alter c-Cbl tyrosine phosphorylation in skeletal muscle of lean or obese rats. However, in contrast to previous studies in adipocytes, c-Cbl tyrosine phosphorylation was reduced after insulin treatment (p<0.001). Conclusions/interpretation: We also found that c-Cbl associating protein expression is relatively low in skeletal muscle of Zucker rats compared to 3T3-L1 adipocytes and this could account for the reduced c-Cbl tyrosine phosphorylation after insulin treatment. Interestingly, basal levels of c-Cbl tyrosine phosphorylation were higher in skeletal muscle from insulin-resistant Zucker rats (p<0.05), but the physiological relevance is not clear. We conclude that the regulation of c-Cbl phosphorylation in skeletal muscle differs from that previously reported in adipocytes.
Pagination412 - 419
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Publication classificationC1 Refereed article in a scholarly journal
Copyright notice2004, Springer-Verlag
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Exercisec-CblInsulin receptorAktZucker ratsScience & TechnologyLife Sciences & BiomedicineEndocrinology & MetabolismSTIMULATED GLUCOSE-TRANSPORTPHOSPHATIDYLINOSITOL 3-KINASETYROSINE PHOSPHORYLATION3T3-L1 ADIPOCYTESGLUT-4 TRANSLOCATIONSIGNAL-TRANSDUCTIONNEGATIVE REGULATOREGF STIMULATIONRECEPTORKINASE