The anti-diabetic AMPK activator AICAR reduces IL-6 and IL-8 in human adipose tissue and skeletal muscle cells

Lihn, Aina S.; Pedersen, Steen B.; Lund, Sten; Richelsen, Bjørn

doi:10.1016/j.mce.2008.06.004

Cited by 58 publications

(53 citation statements)

References 37 publications

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“…54 Likewise, it seems that NDLPCBs also have the ability to downregulate the AMP-activated protein kinase activation 53 ; and the AMP-activated protein kinase inhibits the synthesis of proinflammatory cytokines. 55,56 In addition, endocrine disrupting chemicals may affect the mechanism involved in the risk of hypertension through several different ways. One important pathway is through their direct interaction with the nuclear receptors family.…”

Section: Discussionmentioning

confidence: 99%

Association Between Dietary Intake of Polychlorinated Biphenyls and the Incidence of Hypertension in a Spanish Cohort

et al. 2015

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Polychlorinated biphenyls are persistent organic pollutants that are consumed because of their bioaccumulation through the food chain. Evidence from different sources suggests a positive association between polychlorinated biphenyls exposure and the incidence of hypertension. However, no previous prospective study has investigated this potential relationship in adults. We prospectively assessed the association between dietary intake of polychlorinated biphenyls and the incidence of hypertension in a large cohort. The Seguimiento Universidad de Navarra project is a Spanish cohort of university graduates, most of them health professionals. We included 14521 participants, initially free of hypertension, who were followed-up for a median of 8.3 years. Dietary intake of polychlorinated biphenyls was assessed at baseline through a previously validated 136-item semiquantitative food frequency questionnaire. The published concentration levels of polychlorinated biphenyls measured in samples of food consumed in Spain were used to estimate dietary intake. Multivariable Cox regression models were fitted to estimate hazard ratios and 95% confidence interval for incident hypertension. During follow-up, 1497 incident cases of medically diagnosed hypertension were identified. After adjusting for total energy intake and for potential confounders, participants in the fifth quintile of total polychlorinated biphenyls intake were at higher risk of developing hypertension (adjusted hazard ratio, 1.43 [95% confidence interval, 1.09–1.88; P for trend 0.017]) compared with those in the first quintile. In this Mediterranean cohort, dietary intake of polychlorinated biphenyls, estimated using a food frequency questionnaire, was associated with a higher risk of developing hypertension during follow-up. Nevertheless, further longitudinal studies are needed to confirm our results.

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Section: Discussionmentioning

confidence: 99%

Association Between Dietary Intake of Polychlorinated Biphenyls and the Incidence of Hypertension in a Spanish Cohort

et al. 2015

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“…The activity of AMPK has been proposed as an intracellular signal that governs skeletal muscle cytokine expression (Weigert et al 2007), but another study suggests that AMPK activity is increased by IL6 (Yuen et al 2009). Furthermore, Lihn et al (2008) reported that cytokine expression is reduced by AMPK activity. Clearly, the energy status of the cell, in terms of substrate availability and intracellular signalling, is linked to cytokine expression but exact the nature of the relationship is still not fully understood.…”

Section: The Effect Of Exercise On Cytokine Expressionmentioning

confidence: 99%

Metabolic and endocrine response to exercise: sympathoadrenal integration with skeletal muscle

Ball¹

2014

Journal of Endocrinology

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Skeletal muscle has the capacity to increase energy turnover by w1000 times its resting rate when contracting at the maximum force/power output. Since ATP is not stored in any appreciable quantity, the muscle requires a coordinated metabolic response to maintain an adequate supply of ATP to sustain contractile activity. The integration of intracellular metabolic pathways is dependent upon the cross-bridge cycling rate of myosin and actin, substrate availability and the accumulation of metabolic byproducts, all of which can influence the maintenance of contractile activity or result in the onset of fatigue. In addition, the mobilisation of extracellular substrates is dependent upon the integration of both the autonomic nervous system and endocrine systems to coordinate an increase in both carbohydrate and fat availability. The current review examines the evidence for skeletal muscle to generate power over short and long durations and discusses the metabolic response to sustain these processes. The review also considers the endocrine response from the perspective of the sympathoadrenal system to integrate extracellular substrate availability with the increased energy demands made by contracting skeletal muscle. Finally, the review briefly discusses the evidence that muscle acts in an endocrine manner during exercise and what role this might play in mobilising extracellular substrates to augment the effects of the sympathoadrenal system.

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“…These two proinflammatory mediators are secreted from adipose tissues and play an important role in the etiology of insulin resistance in obese patients. Thus, these effects of AICAR led to the idea that it may serve as a potent drug for increasing insulin sensitivity in peripheral tissues [168]. Nevertheless, AICAR suffers from unfavorable pharmacokinetic properties (i.e., high effective concentration, poor bioavailability and short half life) and severe metabolic complications (e.g., lactic acidosis and massive uric acid production) [169].…”

Section: Aicarmentioning

confidence: 99%

Adenosine Monophosphate-Activated Protein Kinase (AMPK) as a New Target for Antidiabetic Drugs: A Review on Metabolic, Pharmacological and Chemical Considerations

Babai²,

2009

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■ AbstractIn view of the epidemic nature of type 2 diabetes and the substantial rate of failure of current oral antidiabetic drugs the quest for new therapeutics is intensive. The adenosine monophosphate-activated protein kinase (AMPK) is an important regulatory protein for cellular energy balance and is considered a master switch of glucose and lipid metabolism in various organs, especially in skeletal muscle and liver. In skeletal muscles, AMPK stimulates glucose transport and fatty acid oxidation. In the liver, it augments fatty acid oxidation and decreases glucose output, cholesterol and triglyceride synthesis. These metabolic effects induced by AMPK are associated with lowering blood glucose levels in hyperglycemic individuals. Two classes of oral antihyperglycemic drugs (biguanidines and thiazolidinediones) have been shown to exert some of their therapeutic effects by directly or indirectly activating AMPK. However, side effects and an acquired resistance to these drugs emphasize the need for the development of novel and efficacious AMPK activators. We have recently discovered a new class of hydrophobic Dxylose derivatives that activates AMPK in skeletal muscles in a non insulin-dependent manner. One of these derivatives (2,4;3,5-dibenzylidene-D-xylose-diethyl-dithioacetal) stimulates the rate of hexose transport in skeletal muscle cells by increasing the abundance of glucose transporter-4 (GLUT-4) in the plasma membrane through activation of AMPK. This compound reduces blood glucose levels in diabetic mice and therefore offers a novel strategy of therapeutic intervention strategy in type 2 diabetes. The present review describes various classes of chemically-related compounds that activate AMPK by direct or indirect interactions and discusses their potential for candidate antihyperglycemic drug development.

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The anti-diabetic AMPK activator AICAR reduces IL-6 and IL-8 in human adipose tissue and skeletal muscle cells

Cited by 58 publications

References 37 publications

Association Between Dietary Intake of Polychlorinated Biphenyls and the Incidence of Hypertension in a Spanish Cohort

Association Between Dietary Intake of Polychlorinated Biphenyls and the Incidence of Hypertension in a Spanish Cohort

Metabolic and endocrine response to exercise: sympathoadrenal integration with skeletal muscle

Adenosine Monophosphate-Activated Protein Kinase (AMPK) as a New Target for Antidiabetic Drugs: A Review on Metabolic, Pharmacological and Chemical Considerations

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