The effect of insulin and exercise on c-Cbl protein abundance and phosphorylation in insulin-resistant skeletal muscle in lean and obese Zucker rats

The effect of insulin and exercise on c-Cbl protein abundance and phosphorylation in insulin-resistant skeletal muscle in lean and obese Zucker rats

Wadley, G, Bruce, C, Konstantopoulos, N, Macaulay, S, Howlett, K, Hawley, J and Cameron-Smith, D 2004, 'The effect of insulin and exercise on c-Cbl protein abundance and phosphorylation in insulin-resistant skeletal muscle in lean and obese Zucker rats', Diabetologia: clinical and experimental diabetes and metabolism, vol. 47, no. 3, pp. 412-419.

Document type:	Journal Article
Collection:	Journal Articles

Title	The effect of insulin and exercise on c-Cbl protein abundance and phosphorylation in insulin-resistant skeletal muscle in lean and obese Zucker rats
Author(s)	Wadley, G Bruce, C Konstantopoulos, N Macaulay, S Howlett, K Hawley, J Cameron-Smith, D
Year	2004
Journal name	Diabetologia: clinical and experimental diabetes and metabolism
Volume number	47
Issue number	3
Start page	412
End page	419
Total pages	8
Publisher	Springer
Abstract	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 3'-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.
Subject	Endocrinology
Keyword(s)	Protein abundance skeletal muscle Insulin Akt c-Cbl Exercise Insulin receptor Zucker rats
Copyright notice	© Springer-Verlag 2004
ISSN	0012-186X

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