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Appears in Collections:Faculty of Health Sciences and Sport Journal Articles
Peer Review Status: Refereed
Title: Kv1.3 inhibitors have differential effects on glucose uptake and AMPK activity in skeletal muscle cell lines and mouse ex vivo skeletal muscle
Author(s): Hamilton, David Lee
Beall, Craig
Jeromson, Stewart
Chevtzoff, Cyrille
Cuthbertson, Daniel J
Ashford, Michael L J
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Keywords: AMPK
Skeletal muscle
Glucose uptake
Issue Date: Jan-2014
Date Deposited: 3-Mar-2016
Citation: Hamilton DL, Beall C, Jeromson S, Chevtzoff C, Cuthbertson DJ & Ashford MLJ (2014) Kv1.3 inhibitors have differential effects on glucose uptake and AMPK activity in skeletal muscle cell lines and mouse ex vivo skeletal muscle. Journal of Physiological Sciences, 64 (1), pp. 13-20.
Abstract: Knockout of Kv1.3 improves glucose homeostasis and confers resistance to obesity. Additionally, Kv1.3 inhibition enhances glucose uptake. This is thought to occur through calcium release. Kv1.3 inhibition in T-lymphocytes alters mitochondrial membrane potential, and, as many agents that induce Ca2+release or inhibit mitochondrial function activate AMPK, we hypothesised that Kv1.3 inhibition would activate AMPK and increase glucose uptake. We screened cultured muscle with a range of Kv1.3 inhibitors for their ability to alter glucose uptake. Only Psora4 increased glucose uptake in C2C12myotubes. None of the inhibitors had any impact on L6 myotubes. Magratoxin activated AMPK in C2C12myotubes and only Pap1 activated AMPK in the SOL. Kv1.3 inhibitors did not alter cellular respiration, indicating a lack of effect on mitochondrial function. In conclusion, AMPK does not mediate the effects of Kv1.3 inhibitors and they display differential effects in different skeletal muscle cell lines without impairing mitochondrial function.
DOI Link: 10.1007/s12576-013-0285-4
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