Antihyperglycemic effect of equol, a daidzein derivative, in cultured L6 myocytes and <i>ob</i>/<i>ob</i> mice

Cheong, Sun Hee; Furuhashi, Keisuke; Ito, Katsuki; Nagaoka, Masato; Yonezawa, Takayuki; Miura, Yutaka; Yagasaki, Kazumi

doi:10.1002/mnfr.201300272

Cited by 32 publications

(33 citation statements)

References 44 publications

(50 reference statements)

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“…Several studies have reported that antidiabetic natural compounds such as resveratrol and berberine can activate AMPK and that the AMPK activation is important for their antidiabetic action [4,5]. We have also demonstrated that activation of AMPK is involved in the stimulation of glucose uptake induced by natural polyphenols, such as genistein, piceatannol, aspalathin, daidzein, and equol, which improve hyperglycemia in type 2 diabetic model mice [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 68%

“…These changes in GS and PEPCK are considered to increase glucose supply to blood stream and hence induce rises in the blood glucose levels. Some phytochemicals such as aspalathin and equol reversed these changes in hepatic gene expression of GS and PEPCK; the decreased expression of hepatic GS and the increased expression of PEPCK in untreated ob/ob mice were normalized by the treatment of such phytochemicals, leading to reduction of glucose production in the liver of ob/ob mice. In contrast, the hepatic gene expression of GS in db/db mice was significantly increased like that of PEPCK in the current study, and nepodin further increased the expression of GS without affecting that of PEPCK (Figs.…”

Section: Discussionmentioning

confidence: 97%

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Antidiabetic effect of nepodin, a component of Rumex roots, and its modes of action in vitro and in vivo

Yonezawa

Son

et al. 2014

BioFactors

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Many active components derived from edible natural resources such as plant extracts have recently attracted attention for their potential use as functional foods or drugs for preventing and treating metabolic diseases such as diabetes. To obtain a novel modulator of glucose metabolism, we conducted screening of a small compound library in cultured L6 myotubes. We identified nepodin that stimulated glucose uptake dose-dependently in differentiated L6 myotubes. The stimulatory effect of nepodin on glucose uptake was abrogated by a 5'-adenosine monophosphate-activated protein kinase (AMPK) inhibitor. In addition, nepodin stimulated the phosphorylation of AMPK. Nepodin also stimulated the translocation of GLUT4 to the plasma membrane in L6 myoblasts transfected with a Glut4 cDNA-coding vector and in differentiated L6 myotubes. In in vivo study, nepodin suppressed the increases in fasting blood glucose levels and improved the glucose intolerance of C57BL/KsJ-db/db mice, a type 2 diabetic animal model. Nepodin rescued the impaired phosphorylation of AMPK in the skeletal muscle of db/db mice. These results suggest that nepodin has an antidiabetic effect, which is at least partly mediated by stimulation of GLUT4 translocation via AMPK activation by nepodin.

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Section: Introductionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 97%

Antidiabetic effect of nepodin, a component of Rumex roots, and its modes of action in vitro and in vivo

Yonezawa

Son

et al. 2014

BioFactors

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“…However, more recently attention has also been given to its metabolites, like desmethylangolensin (DMA), dihydrodaidzein (DHD), and cis‐4‐OH‐equol, which are formed by intestinal bacteria . Among the daidzein metabolites, equol has been known to be very effective in the regulation of T2D . Several animal and human studies have been conducted to investigate the antidiabetic action of daidzein and its derivatives.…”

Section: Introductionmentioning

confidence: 99%

Daidzein, its effects on impaired glucose and lipid metabolism and vascular inflammation associated with type 2 diabetes

et al. 2018

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Over the last decades, the incidence of type 2 diabetes (T2D) is increasing substantially. Emerging evidences from epidemiological studies have shown the association between higher intake of soy isoflavones and reduced risk of T2D and its associated health risks. Daidzein, a soy isoflavone, has been found to have a promising therapeutic potential in managing T2D pathophysiology. Fermented soybean is the major source of daidzein; however, it can also be formed via the consumption of its glycosylated moiety, daidzin with subsequent hydrolysis by intestinal bacterial enzyme. Many studies reported the prophylactic effect of daidzein on the improvement of hyperglycemia, insulin resistance, dislipidemia, obesity, inflammation, and other complications associated with T2D. The molecular mechanisms underlying the action of daidzein include diverged pathways where daidzein has been shown to interact with several signaling molecules and receptors to achieve desirable effect. Although the specific molecular mechanism is still elusive, further studies are thus needed to understand it in detail. In this review, we discuss the antidiabetic potential of daidzein with respect to the evidences from various clinical, preclinical, and cell culture studies and the underlying molecular mechanism in a precise way to have a comprehensive account on this isoflavone with promising therapeutic potential. © 2018 BioFactors, 44(5):407-417, 2018.

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“…There is increasing evidence that soy food has antidiabetic effects. Equol was recently found to have an antihyperglycemic effect in T2DM model mice (27) although its effect on b-cell function remains unclear. The soy isoflavone genistein has been proposed as an agent to protect b-cell function and to prevent b-cell injury (28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

S-Equol Enantioselectively Activates cAMP-Protein Kinase A Signaling and Reduces Alloxan-Induced Cell Death in INS-1 Pancreatic ^|^beta;-Cells

Horiuchi

Harada

Adachi

et al. 2014

J Nutr Sci Vitaminol

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Summary S-Equol is enantioselectively produced from the isoflavone daidzein by gut microflora and is absorbed by the body. An increase of pancreatic b-cell death is directly associated with defects in insulin secretion and an increased risk of type 2 diabetes mellitus. In the present study, we demonstrate that only the S-enantiomer has suppressive effects against alloxan-induced oxidative stress in INS-1 pancreatic b-cells. S-Equol reduced alloxan-induced cell death in a dose-dependent manner, whereas R-equol had no effects. In contrast, no significant differences were observed between the enantiomers in estrogenic activity. The cytoprotective effects of S-equol were stronger than those of its precursor daidzein and were blocked by the protein synthesis inhibitor cycloheximide. The cytoprotection was diminished when cells were incubated with a protein kinase A (PKA) inhibitor (H89), but not an estrogen receptor inhibitor. S-Equol increased intracellular cAMP levels in an enantioselective manner. S-Equol, but not R-equol, induced phosphorylation of cAMPresponse element-binding protein at Ser 133, and induced cAMP-response element-mediated transcription, both of which were diminished in the presence of H89. Taken together, these results show that S-equol enantioselectively increases the survival of INS-1 cells presumably through activating PKA signaling. Thus, S-equol might have applications as an anti-type 2 diabetic agent. Key Words equol, cAMP, protein kinase A signaling, enantioselectivity, pancreatic b-cells * To whom correspondence should be addressed. E-mail: harada@biochem.osakafu-u.ac.jp Abbreviations: CHX, cycloheximide; CRE, cAMP response element; CREB, cAMP-response element-binding protein; E2, 17b-estradiol; ER, estrogen receptor; PKA, protein kinase A; RLU, relative light units; T2DM, type 2 diabetes mellitus.

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Antihyperglycemic effect of equol, a daidzein derivative, in cultured L6 myocytes and ob/ob mice

Cited by 32 publications

References 44 publications

Antidiabetic effect of nepodin, a component of Rumex roots, and its modes of action in vitro and in vivo

Antidiabetic effect of nepodin, a component of Rumex roots, and its modes of action in vitro and in vivo

Daidzein, its effects on impaired glucose and lipid metabolism and vascular inflammation associated with type 2 diabetes

S-Equol Enantioselectively Activates cAMP-Protein Kinase A Signaling and Reduces Alloxan-Induced Cell Death in INS-1 Pancreatic ^|^beta;-Cells

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