The activation of p38 MAPK by the β‐adrenergic agonist isoproterenol in rat epididymal fat cells

Moule, S K; Denton, Richard M.

doi:10.1016/s0014-5793(98)01392-1

Cited by 106 publications

(88 citation statements)

References 35 publications

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“…Consistent with the latter, a ␤-adrenergic agonist activates AMPK in brown (17) and white adipocytes (16) in vitro and ex vivo (18).…”

Section: Discussionsupporting

confidence: 64%

“…Materials-Phentolamine, propranolol, and isoproterenol were purchased from Sigma, AKT inhibitor (10-DEBC) was purchased from Tocris USA, and PKA inhibitor (PKA-I, [14][15][16][17][18][19][20][21][22] was purchased from Calbiochem.…”

Section: Methodsmentioning

confidence: 99%

“…The effects of leptin through the hypothalamus on muscle AMPK involve ␣-adrenergic receptors in muscle (8). The ␣-adrenergic agonist, phenylephrine, activates AMPK in isolated soleus muscle, C2C12 myocytes, and CHO cells (8,14,15), whereas the ␤-adrenergic agonist, isoproterenol, stimulates AMPK in isolated adipocytes (16). Norepinephrine and epinephrine, both dual ␣ and ␤ agonists, activate AMPK in brown adipocytes in vitro (17) and white adipocytes ex vivo (18), and in the latter, activation of AMPK was necessary for maximal activation of lipolysis (18).…”

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confidence: 99%

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Adrenergic Regulation of AMP-activated Protein Kinase in Brown Adipose Tissue in Vivo

Pulinilkunnil

Kong

et al. 2011

Journal of Biological Chemistry

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AMP-activated protein kinase (AMPK), an evolutionarily conserved serine-threonine kinase that senses cellular energy status, is activated by stress and neurohumoral stimuli. We investigated the mechanisms by which adrenergic signaling alters AMPK activation in vivo. Brown adipose tissue (BAT) is highly enriched in sympathetic innervation, which is critical for regulation of energy homeostasis. We performed unilateral denervation of BAT in wild type (WT) mice to abolish neural input. Six days post-denervation, UCP-1 protein levels and AMPK ␣2 protein and activity were reduced by 45%. In ␤ 1,2,3 -adrenergic receptor knock-out mice, unilateral denervation led to a 25-45% decrease in AMPK activity, protein expression, and Thr 172 phosphorylation. In contrast, acute ␣-or ␤-adrenergic blockade in WT mice resulted in increased AMPK ␣ Thr 172 phosphorylation and AMPK ␣1 and ␣2 activity in BAT. But short term blockade of ␣-adrenergic signaling in ␤ 1,2,3 -adrenergic receptor knock-out mice resulted in decreased AMPK activity in BAT, which strongly correlated with enhanced phosphorylation of AMPK on Ser 485/491 , a site associated with inhibition of AMPK activity. Both PKA and AKT inhibitors attenuated AMPK Ser 485/491 phosphorylation resulting from ␣-adrenergic blockade and prevented decreases in AMPK activity. In vitro mechanistic studies in BAT explants showed that the effects of ␣-adrenergic blockade appeared to be secondary to inhibition of oxygen consumption. In conclusion, adrenergic pathways regulate AMPK activity in vivo acutely via alterations in Thr 172 phosphorylation and chronically through changes in the ␣ catalytic subunit protein levels. Furthermore, AMPK ␣ Ser 485/491 phosphorylation may be a novel mechanism to inhibit AMPK activity in vivo and alter its biological effects. AMP-activated protein kinase (AMPK),4 an evolutionarily conserved serine threonine kinase, is a fuel-sensing enzyme complex activated by cellular stresses that increase AMP or deplete ATP including hypoxia, ischemia, glucose deprivation, uncouplers of oxidative phosphorylation, exercise, and muscle contraction (1, 2). Once activated, AMPK phosphorylates multiple downstream substrates that function to preserve the AMP: ATP ratio through inhibition of ATP-catabolizing pathways and promotion of ATP-generating pathways. Mechanisms involved in AMPK activation include 1) binding of AMP to an allosteric site on the ␥ subunit, which renders the holoenzyme resistant to inactivating serine phosphatases and may also have direct allosteric effects on kinase activity (1, 2) and 2) phosphorylation by upstream AMPK kinases of the ␣ (catalytic) subunits on Thr 172 , which is essential for kinase activity. Recent studies employing INS-1 cells (3), hepatitis C virus harboring replicon cells (4), and isolated heart preparations (5) have demonstrated another potential regulatory mechanism; that is, AMPK may also undergo inhibitory phosphorylation on serine 485 and 491 residues of the ␣1 and ␣2 catalytic subunits, respectively. Some data suggest that upstr...

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“…Consistent with the latter, a ␤-adrenergic agonist activates AMPK in brown (17) and white adipocytes (16) in vitro and ex vivo (18).…”

Section: Discussionsupporting

confidence: 64%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Adrenergic Regulation of AMP-activated Protein Kinase in Brown Adipose Tissue in Vivo

Pulinilkunnil

Kong

et al. 2011

Journal of Biological Chemistry

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“…One can also entertain the interesting possibility that, in skeletal muscle, this substrate cycling is also activated in response to other hormones and neurotransmitters (eg, adiponectin, catecholamines) particularly since adiponectin, as well as adrenergic agonists, can also stimulate AMPK activity, glucose utilization and fatty acid oxidation in skeletal muscle or adipose tissue. 61,[66][67][68][69] This substrate cycling between de novo lipogenesis and lipid oxidation could therefore constitute a thermogenic effector in skeletal muscle. Theoretically, the synthesis of one molecule of palmitic acid from acetyl-CoA and its re-oxidation to acetylCoA would cost at least 14 molecules of ATP.…”

Section: Substrate Cycling Between De Novo Lipogenesis and Lipid Oxidmentioning

confidence: 99%

Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity

et al. 2004

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Life is a combustion, but how the major fuel substrates that sustain human life compete and interact with each other for combustion has been at the epicenter of research into the pathogenesis of insulin resistance ever since Randle proposed a 'glucose-fatty acid cycle' in 1963. Since then, several features of a mutual interaction that is characterized by both reciprocality and dependency between glucose and lipid metabolism have been unravelled, namely:(i) the inhibitory effects of elevated concentrations of fatty acids on glucose oxidation (via inactivation of mitochondrial pyruvate dehydrogenase or via desensitization of insulin-mediated glucose transport), (ii) the inhibitory effects of elevated concentrations of glucose on fatty acid oxidation (via malonyl-CoA regulation of fatty acid entry into the mitochondria), and more recently (iii) the stimulatory effects of elevated concentrations of glucose on de novo lipogenesis, that is, synthesis of lipids from glucose (via SREBP1c regulation of glycolytic and lipogenic enzymes).This paper first revisits the physiological significance of these mutual interactions between glucose and lipids in skeletal muscle pertaining to both blood glucose and intramyocellular lipid homeostasis. It then concentrates upon emerging evidence, from calorimetric studies investigating the direct effect of leptin on thermogenesis in intact skeletal muscle, of yet another feature of the mutual interaction between glucose and lipid oxidation: that of substrate cycling between de novo lipogenesis and lipid oxidation. It is proposed that this energy-dissipating substrate cycling that links glucose and lipid metabolism to thermogenesis could function as a 'fine-tuning' mechanism that regulates intramyocellular lipid homeostasis, and hence contributes to the protection of skeletal muscle against lipotoxicity.

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“…In fat cells, activation of AMPK as been proposed to limit fatty acid efflux and to favour local fatty acid oxidation, thus lowering circulating free fatty acids levels (Daval et al, 2005). However, contrary findings (Moule and Denton, 1998;Yin et al, 2003) have suggested that -adrenergic agonists act to increase the phosphorylation of AMPK at Thr-172 perhaps via cAMP-stimulated phosphorylation, an event which, from the use of a dominantnegative form of AMPK, implied that AMPK activation was required for maximal stimulation of lipolysis. In contrast to skeletal muscle, activation of AMPK has been reported to inhibit , to activate (Yamaguchi et al, 2005) or to have no effect on (Chavez et al, 2008) fat cell Glut4 translocation and glucose transport.…”

Section: Role Of Ampk Activation In Insulin-target Tissuesmentioning

confidence: 99%

The AMP-regulated kinase family: Enigmatic targets for diabetes therapy

Rutter

Leclerc

2009

Molecular and Cellular Endocrinology

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Please cite this article as: Rutter, G.A., Leclerc, I., The AMP-regulated kinase family: enigmatic targets for diabetes therapy, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Pt 1):1-16, 2003). In the subsequent five years, dramatic strides have taken place in our understanding of the role of AMPK in the control of whole body metabolic homeostasis, the regulation of the enzyme by upstream kinases, and its molecular structure.These new studies and earlier work arguably propel AMPK, and perhaps related family members into a "super league" of potential therapeutic targets for maladies including diabetes, cancer, heart disease, and obesity. Here we survey some of these recent advances, focussing on the role of this and related enzymes in the control of pancreatic β-cell function and glucose homeostasis.

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The activation of p38 MAPK by the β‐adrenergic agonist isoproterenol in rat epididymal fat cells

Cited by 106 publications

References 35 publications

Adrenergic Regulation of AMP-activated Protein Kinase in Brown Adipose Tissue in Vivo

Adrenergic Regulation of AMP-activated Protein Kinase in Brown Adipose Tissue in Vivo

Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity

The AMP-regulated kinase family: Enigmatic targets for diabetes therapy

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