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Cultured muscle cells from insulin-resistant type 2 diabetes patients have impaired insulin, but normal 5-amino-4-imidazolecarboxamide riboside-stimulated, glucose uptake

Lookup NU author(s): Dr Elizabeth McIntyre, Dr Reza Halse, Professor Steve Yeaman, Professor Mark Walker

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Abstract

Impaired insulin action is a characteristic feature of type 2 diabetes. The study aims were to investigate whether after prolonged culture skeletal muscle cultures from insulin-resistant, type 2 diabetic patients (taking >100 U insulin/d) displayed impaired insulin signaling effects compared with cultures from nondiabetic controls and to determine whether retained abnormalities were limited to insulin action by studying an alternative pathway of stimulated glucose uptake. Studies were performed on myotubes differentiated for 7 d between passages 4 and 6. Insulin-stimulated glucose uptake (100 nM; P < 0.05) and insulin-stimulated glycogen synthesis (1 nM; P < 0.01) were significantly impaired in the diabetic vs. control cultures. Protein kinase B (PKB) expression and phosphorylated PKB levels in response to insulin stimulation (20 DM) were comparable in the diabetic and control cultures. 5-Amino-4-imidazolecarboxamide riboside (AICAR) mimics the effect of exercise on glucose uptake by activating AMP-activated protein kinase. There was no difference in AICAR (2 mM)-stimulated glucose uptake between diabetic vs. control myotube cultures (P = not significant). In conclusion, diabetic muscle cultures retain signaling defects after prolonged culture that appear specific to the insulin signaling pathway, but not involving PKB. This supports an intrinsic abnormality of the diabetic muscle cells that is most likely to have a genetic basis.


Publication metadata

Author(s): McIntyre EA, Halse R, Yeaman SJ, Walker M

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology and Metabolism

Year: 2004

Volume: 89

Issue: 7

Pages: 3440-3448

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: The Endocrine Society

URL: http://dx.doi.org/10.1210/jc.2003-031919

DOI: 10.1210/jc.2003-031919

PubMed id: 15240629


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