NFAT-133 increases glucose uptake in L6 myotubes by activating AMPK pathway

Thakkar, Chandni; Kate, Abhijeet S.; Desai, Dattatraya C.; Ghosh, Asit Ranjan; Kulkarni-Almeida, Asha

doi:10.1016/j.ejphar.2015.11.006

Cited by 18 publications

(33 citation statements)

References 34 publications

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“…17β-estradiol pretreatment decreased the mRNA and protein expression of the myometrial α 2 -AR subtypes and (-)-noradrenaline-evoked myometrial contraction via the α 2 -ARs, which is similar to our earlier findings with α 1A -ARs ( 14 ). According to these findings, we can claim that estrogen differently affects the expression of the α 2 -ARs in various tissues, as it increases the expression of the receptors in the spinal cord and cutaneous arteries ( 27 , 28 ).…”

Section: Discussionsupporting

confidence: 90%

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The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro

et al. 2016

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AimTo assess the effect of 17β-estradiol pretreatment on the function and expression of α2- adrenergic receptors (ARs) subtypes in late pregnancy in rats.MethodsSprague-Dawley SPD rats (n = 37) were treated with 17β-estradiol for 4 days starting from the 18th day of pregnancy. The myometrial expression of the α2-AR subtypes was determined by real time polymerase chain reaction and Western blot analysis. In vitro contractions were stimulated with (-)-noradrenaline, and its effect was modified with the selective antagonists BRL 44408 (α2A), ARC 239 (α2B/C), and spiroxatrine (α2A). The cyclic adenosine monophosphate (cAMP) accumulation was also measured. The activated G-protein level was investigated by guanosine 5′-O-[gamma-thio]triphosphate (GTPγS) binding assay.Results17β-estradiol pretreatment decreased the contractile effect of (-)-noradrenaline via the α2-ARs, and abolished the contractile effect via the α2B-ARs. All the α2-AR subtypes’ mRNA was significantly decreased. 17β-estradiol pretreatment significantly increased the myometrial cAMP level in the presence of BRL 44408 (P = 0.001), ARC 239 (P = 0.007), and spiroxatrine (P = 0.045), but did not modify it in the presence of spiroxatrine + BRL 44408 combination (P = 0.073). It also inhibited the G-protein-activating effect of (-)-noradrenaline by 25% in the presence of BRL 44408 + spiroxatrine combination.ConclusionsThe expression of the α2-AR subtypes is sensitive to 17β-estradiol, which decreases the contractile response of (-)-noradrenaline via the α2B-AR subtype, and might cause changes in G-protein signaling pathway. Estrogen dysregulation may be responsible for preterm labor or uterine inertia via the α2-ARs.

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Section: Discussionsupporting

confidence: 90%

“…Myometrial α 1 -AR expression is influenced by female sexual steroid hormones, mainly estrogens. 17β-estradiol decreases the expression of the α 1A -ARs, but does not influence the expression of α 1D -ARs ( 14 ). However, the effect of estrogens on the myometrial α 2 -AR subtypes is unknown.…”

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confidence: 99%

The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro

et al. 2016

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“…However, Protocatechuic acid treatment significantly increased the IRS1 phosphorylation, PI3K (p85) expression, Akt phosphorylation, and GLUT4 expression in T2D rats. AMPK regulates cellular energy homeostasis in glucose utilization process (Thakkar et al, 2015). Protocatechuic acid significantly activated AMPK phosphorylation (Thr 172) and thereby regulates cellular energy homeostasis in glucose utilization in the T2D rats.…”

Section: Discussionmentioning

confidence: 99%

Protocatechuic Acid, a Phenolic from Sansevieria roxburghiana Leaves, Suppresses Diabetic Cardiomyopathy via Stimulating Glucose Metabolism, Ameliorating Oxidative Stress, and Inhibiting Inflammation

et al. 2017

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Persistent hyperglycemia, impairment of redox status and establishment of inflammatory pathophysiology integrally play important role in the pathogenesis of diabetic cardiomyopathy (DC). Present study examined the therapeutic potential of protocatechuic acid isolated from the Sansevieria roxburghiana rhizomes against DC employing rodent model of type 2 diabetes (T2D). T2D was induced by high fat diet + a low-single dose of streptozotocin (35 mg/kg, i.p.). T2D rats exhibited significantly (p < 0.01) high fasting blood glucose level. Alteration in serum lipid profile (p < 0.01) and increased levels of lactate dehydrogenase (p < 0.01) and creatine kinase (p < 0.01) in the sera of T2D rats revealed the occurrence of hyperlipidemia and diabetic pathophysiology. A significantly (p < 0.01) high levels of serum C-reactive protein and pro-inflammatory mediators revealed the establishment of inflammatory occurrence in T2D rats. Besides, significantly high levels of troponins in the sera revealed the establishment of cardiac dysfunctions in T2D rats. However, protocatechuic acid (50 and 100 mg/kg, p.o.) treatment could significantly reverse the changes in serum biochemical parameters related to cardiac dysfunctions. Molecular mechanism studies demonstrated impairment of signaling cascade, IRS1/PI3K/Akt/AMPK/p 38/GLUT4, in glucose metabolism in the skeletal muscle of T2D rats. Significant (p < 0.01) activation of polyol pathway, enhanced production of AGEs, oxidative stress and up-regulation of inflammatory signaling cascades (PKC/NF-κB/PARP) were observed in the myocardial tissue of T2D rats. However, protocatechuic acid (50 and 100 mg/kg, p.o.) treatment could significantly (p < 0.05–0.01) stimulate glucose metabolism in skeletal muscle, regulated glycemic and lipid status, reduced the secretion of pro-inflammatory cytokines, and restored the myocardial physiology in T2D rats near to normalcy. Histological assessments were also in agreement with the above findings. In silico molecular docking study again supported the interactions of protocatechuic acid with different signaling molecules, PI3K, IRS, Akt, AMPK PKC, NF-κB and PARP, involved in glucose utilization and inflammatory pathophysiology. In silico ADME study predicted that protocatechuic acid would support the drug-likeness character. Combining all, results would suggest a possibility of protocatechuic acid to be a new therapeutic agent for DC in future.

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“…12 Detailed mechanistic investigations revealed that NFAT-133 decreases the mitochondrial membrane potential in a dose-dependent manner, which leads to a reduced ATP production and, consequently, an increase of the AMP : ATP ratio. 13 NFAT-133 was also isolated from Streptomyces sp. K07-0010 along with the two structurally related isochromans panowamyin A and B, and displayed moderate antitrypanosomal activity.…”

Section: Introductionmentioning

confidence: 99%

Antidiabetic profiling of veramycins, polyketides accessible by biosynthesis, chemical synthesis and precursor-directed modification

et al. 2022

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NFAT-133 increases glucose uptake in L6 myotubes by activating AMPK pathway

Cited by 18 publications

References 34 publications

The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro

The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro

Protocatechuic Acid, a Phenolic from Sansevieria roxburghiana Leaves, Suppresses Diabetic Cardiomyopathy via Stimulating Glucose Metabolism, Ameliorating Oxidative Stress, and Inhibiting Inflammation

Antidiabetic profiling of veramycins, polyketides accessible by biosynthesis, chemical synthesis and precursor-directed modification

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