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Impaired enhancement of insulin action in cultured skeletal muscle cells from insulin resistant type 2 diabetic patients in response to contraction using electrical pulse stimulation

Lookup NU author(s): Ali Al-Bayati, Dr Audrey Brown, Professor Mark Walker

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Abstract

© 2019 Elsevier Inc. Aims: Skeletal muscle insulin resistance is a characteristic feature of type 2 diabetes. The aim of this study was to examine the effect of contraction on insulin action using electrical pulse stimulation (EPS) in cultured skeletal muscle cells from insulin resistant type 2 diabetic patients. Methods: Skeletal muscle cell cultures were established from 6 insulin resistant type 2 diabetic subjects and age and BMI matched non-diabetic control subjects. Day 7 differentiated myotubes were treated with or without EPS for 16 h, after which glucose uptake and AS160 phosphorylation were measured in the presence or absence of insulin. Results: In control myotubes, EPS resulted in increased phosphorylation of AMPKThr172 (vs no EPS; p < 0.01), and this was associated with increased glucose uptake (p < 0.05). Insulin in the absence of EPS increased glucose uptake and AS160Thr642 phosphorylation, and both effects were significantly enhanced by prior EPS. In the absence of EPS, AMPK activation was significantly increased (p < 0.01) in the diabetic vs control myotubes. Despite a comparable degree of AMPK activation following EPS, the action of insulin on glucose uptake (p < 0.05) and AS160Thr642 phosphorylation (p < 0.001) was decreased in the diabetic vs control myotubes. Conclusion: EPS mediated AMPK activation enhances the effect of insulin on glucose uptake and AS160Thr642 phosphorylation in control myotubes replicating key metabolic benefits of exercise on insulin action in man. Conversely, insulin mediated glucose uptake and AS160Thr642 phosphorylation remain significantly decreased in diabetic vs control myotubes despite a comparable degree of AMPK activation following EPS.


Publication metadata

Author(s): Al-bayati A, Brown A, Walker M

Publication type: Article

Publication status: Published

Journal: Journal of Diabetes and its Complications

Year: 2019

Pages: Epub ahead of print

Online publication date: 01/08/2019

Acceptance date: 29/07/2019

ISSN (print): 1056-8727

ISSN (electronic): 1873-460X

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.jdiacomp.2019.107412

DOI: 10.1016/j.jdiacomp.2019.107412


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