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Lookup NU author(s): Dr Audrey Brown,
Emeritus Professor Steve Yeaman,
Professor Mark Walker
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Calpain-10 was identified as a novel type 2 diabetes susceptibility gene, although the mechanisms by which it increases susceptibility to type 2 diabetes remain unclear. As skeletal muscle is the principal site of the peripheral insulin resistance for glucose disposal in type 2 diabetes, we investigated whether targeted suppression of calpain-10 expression directly affects insulin action in cultured human skeletal muscle cells. Short interfering RNAs (siRNAs) were employed to specifically suppress CAPN10 gene expression. Suppression was seen at both the transcript and protein level, as assessed by quantitative PCR and Western blotting. Suppression of CAPN10 mRNA expression (75% decrease compared to untransfected myotubes) was associated with a significant decrease (p = 0.04) in insulin-stimulated glucose uptake (1.03 ± 0.06 [mean ± SEM]-fold increase over basal) compared to the untransfected myotubes (1.43 ± 0.16-fold increase). In contrast, decreased suppression of calpain-10 expression did not affect insulin-stimulated glycogen synthesis nor insulin-stimulated phosphorylation of protein kinase B, a key component of the insulin-signalling pathway. This study confirms that calpain-10 plays a role in insulin-stimulated glucose uptake in human skeletal muscle cells. Suppression of calpain-10 expression did not affect insulin-stimulated glycogen synthesis nor insulin-signalling via PKB, suggesting that calpain-10 may exert a direct regulatory effect upon the glucose uptake mechanism. © 2007 Elsevier Inc. All rights reserved.
Author(s): Brown AE, Yeaman SJ, Walker M
Publication type: Article
Publication status: Published
Journal: Molecular Genetics and Metabolism
ISSN (print): 1096-7192
ISSN (electronic): 1096-7206
Publisher: Academic Press
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