α-Lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle

Lee, Woo Je; Song, Kee‐Ho; Koh, Eun Hee; Won, Jong Chul; Kim, Hyoun Sik; Park, Hye-Sun; Kim, Min‐Seon; Kim, Seung Whan; Lee, Ki‐Up; Park, Joong‐Yeol

doi:10.1016/j.bbrc.2005.05.035

Cited by 204 publications

(138 citation statements)

References 41 publications

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“…Second, AMPK activation by t-RVT definitely potentiated the insulin-induced Akt activation ( Figure 4B), leading to improvement of insulin sensitivity. Quite similar to our results, a couple of recent studies demonstrated that -lipoic acid as well as metformin has been reported to improve insulin sensitivity by activating AMPK (Kumar and Dey, 2002;Lee et al, 2005). Despite many efforts, the mechanism by which AMPK increase insulin sensitivity remains almost unknown.…”

Section: Discussionsupporting

confidence: 90%

“…Thiazolindinediones (TZDs), another antidiabetic drugs which are specific ligands for peroxisome proliferator-activated receptor-, has also been shown to improve insulin sensitivity by activating AMPK . In addition, antiobesitic effect of leptin, adiponectin, and -lipoic acid is mediated by AMPK Yamauchi et al, 2002;Lee et al, 2005). Therefore, AMPK is thought to be a novel therapeutic target to reduce blood glucose levels in type 2 diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMP-activated protein kinase

Park

Kim²,

Lee³

et al. 2007

Exp Mol Med

213

144

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trans-Resveratrol (t-RVT), a naturally occurring polyphenol found in Polygonum cuspidatum, grape, and red wine, has been reported to have antiinflammatory, cardioprotective, and cancer chemopreventive properties. However antidiabetic effect of t-RVT has not yet been reported. In this study, we show that t-RVT increases glucose uptake in C2C12 myotubes by activating AMP-activated protein kinase (AMPK), uncovering an antidiabetic potential of t-RVT for the first time. AMPK plays a central role in the regulation of glucose and lipid metabolism, and hence it is considered a novel therapeutic target for metabolic syndrome such as type 2 diabetes. t-RVT significantly induced glucose uptake in C2C12 cells, via AMPK activation, but not a phosphatidylinositol-3 kinase (PI-3 kinase) signal pathway. The induced glucose uptake was attenuated by pretreatment with a pharmacological inhibitor for AMPK, indicating that the effect of t-RVT primarily depends on AMPK activation. However, in the presence of insulin, t-RVT also potentiated the effect of insulin on glucose uptake via AMPK activation, which led to further activation of PI-3 kinase/Akt signal pathway.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMP-activated protein kinase

Park

Kim²,

Lee³

et al. 2007

Exp Mol Med

213

144

View full text Add to dashboard Cite

show abstract

“…All secretion and total insulin data were normalised to total DNA and are expressed as means±SE. *p<0.05; **p<0.01; ***p<0.001 compared with controls α-LA acted as an insulin sensitiser in skeletal muscle [38], and prevented endothelial cell dysfunction in obese rats [39], effects shown to be attributable to AMPK activation. Thus, it is likely that AMPK is responsible for many of the diverse antidiabetic effects of this compound.…”

Section: Discussionmentioning

confidence: 91%

α-Lipoic acid regulates AMP-activated protein kinase and inhibits insulin secretion from beta cells

et al. 2006

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Aims/hypothesis: The antioxidant compound α-lipoic acid (α-LA) possesses antidiabetic and anti-obesity properties. In the hypothalamus, α-LA suppresses appetite and prevents obesity by inhibiting AMP-activated protein kinase (AMPK). Given the therapeutic potential of α-LA for the treatment of type 2 diabetes and obesity, and the importance of AMPK in beta cells, we examined the effect of α-LA on pancreatic beta cell function. Materials and methods: Isolated rat islets and MIN6 beta cells were treated acutely (15-90 min) or chronically (18-24 h) with α-LA or the known AMPK-activating compounds 5′-amino-imidazole-4-carboxamide ribonucleoside (AICAR) and metformin. Insulin secretion, the AMPK-signalling pathway, mitochondrial function and cell growth were assessed. Results: Acute or chronic treatment of islets and MIN6 cells with α-LA led to dose-dependent rises in phosphorylation of the AMPK α-subunit and acetyl CoA carboxylase. Chronic exposure to α-LA, AICAR or metformin caused a reduction in insulin secretion. α-LA inhibited the p70 s6 kinase translational control pathway, and inhibited MIN6 growth in a manner similar to rapamycin. Unlike AICAR and metformin, α-LA also acutely inhibited insulin secretion. Examination of the effect of α-LA on mitochondrial function showed that acute treatment with this compound elevated reactive oxygen species (ROS) production and enhanced mitochondrial depolarisation induced by Ca 2+ . Conclusions/ interpretation: This study is the first to demonstrate that α-LA directly affects beta cell function. The chronic effects of α-LA include AMPK activation and reductions in insulin secretion and content, and cell growth. Acutely, α-LA also inhibits insulin secretion, an effect probably involving the ROS-induced impairment of mitochondrial function.

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“…Dysfunction of AMPK activity may lead to metabolic syndrome. There is correlation between the low activation state of AMPK with metabolic disorders associated with insulin resistance and obesity (23,24). AMPK activity is also suppressed in muscle and liver by sustained hyperglycemia (25).…”

Section: Discussionmentioning

confidence: 99%

E3 Ubiquitin Ligase, WWP1, Interacts with AMPKα2 and Down-regulates Its Expression in Skeletal Muscle C2C12 Cells

Lee

Kim

et al. 2013

Journal of Biological Chemistry

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Background:The role of the ubiquitin-proteasome pathway under high glucose conditions is unclear. Results: AMPK␣2 interacts with WWP1, and its expression is down-regulated by the ubiquitin proteasome pathway in high glucose culture conditions in C2C12 cells. Conclusion: WWP1 down-regulates AMPK␣2 expression through direct interaction in high glucose culture conditions of skeletal muscle C2C12 cells. Significance: The ubiquitin proteasome pathway may involve high glucose-induced AMPK␣2 down-regulation.

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α-Lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle

Cited by 204 publications

References 41 publications

Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMP-activated protein kinase

Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMP-activated protein kinase

α-Lipoic acid regulates AMP-activated protein kinase and inhibits insulin secretion from beta cells

E3 Ubiquitin Ligase, WWP1, Interacts with AMPKα2 and Down-regulates Its Expression in Skeletal Muscle C2C12 Cells

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