TY - JOUR
T1 - AMPK and insulin action
T2 - Responses to ageing and high fat diet
AU - Frøsig, Christian
AU - Jensen, Thomas Elbenhardt
AU - Jeppesen, Jacob
AU - Pehmøller, Christian
AU - Treebak, Jonas Thue
AU - Maarbjerg, Stine Just
AU - Kristensen, Jonas Møller
AU - Sylow, Lykke
AU - Alsted, Thomas Junker
AU - Schjerling, Peter
AU - Kiens, Bente
AU - Wojtaszewski, Jørgen
AU - Richter, Erik A.
N1 - CURIS 2013 NEXS 104
PY - 2013
Y1 - 2013
N2 - The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact role of AMPK is not well understood. Here we hypothesized that mice lacking a2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (~4 month) or old (~18 month) wild type and muscle specific a2AMPK kinase-dead mice on chow diet as well as old mice on 17 weeks of high fat diet were studied for whole body glucose homeostasis (OGTT, ITT and HOMA-IR), insulin signaling and insulin-stimulated glucose uptake in muscle. We demonstrate that high fat diet in old mice results in impaired glucose homeostasis and insulin stimulated glucose uptake in both the soleus and extensor digitorum longus muscle, coinciding with reduced insulin signaling at the level of Akt (pSer473 and pThr308), TBC1D1 (pThr590) and TBC1D4 (pThr642). In contrast to our hypothesis, the impact of ageing and high fat diet on insulin action was not worsened in mice lacking functional a2AMPK in muscle. It is concluded that a2AMPK deficiency in mouse skeletal muscle does not cause muscle insulin resistance in young and old mice and does not exacerbate obesity-induced insulin resistance in old mice suggesting that decreased a2AMPK activity does not increase susceptibility for insulin resistance in skeletal muscle.
AB - The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact role of AMPK is not well understood. Here we hypothesized that mice lacking a2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (~4 month) or old (~18 month) wild type and muscle specific a2AMPK kinase-dead mice on chow diet as well as old mice on 17 weeks of high fat diet were studied for whole body glucose homeostasis (OGTT, ITT and HOMA-IR), insulin signaling and insulin-stimulated glucose uptake in muscle. We demonstrate that high fat diet in old mice results in impaired glucose homeostasis and insulin stimulated glucose uptake in both the soleus and extensor digitorum longus muscle, coinciding with reduced insulin signaling at the level of Akt (pSer473 and pThr308), TBC1D1 (pThr590) and TBC1D4 (pThr642). In contrast to our hypothesis, the impact of ageing and high fat diet on insulin action was not worsened in mice lacking functional a2AMPK in muscle. It is concluded that a2AMPK deficiency in mouse skeletal muscle does not cause muscle insulin resistance in young and old mice and does not exacerbate obesity-induced insulin resistance in old mice suggesting that decreased a2AMPK activity does not increase susceptibility for insulin resistance in skeletal muscle.
U2 - 10.1371/journal.pone.0062338
DO - 10.1371/journal.pone.0062338
M3 - Journal article
C2 - 23671593
VL - 8
SP - e62338
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 5
ER -