Mechanisms of Genistein Protection on Pancreas Cell Damage in High Glucose Condition

Zhong, Wu; Liu, Yang; Li, Chunlin

doi:10.2169/internalmedicine.50.5320

Cited by 13 publications

(8 citation statements)

References 25 publications

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“…In human islets, 100 µM genistein prevented high-glucose (24 h incubation) mediated cell damage by off-setting reductions in cell growth and DNA fragmentation 109 . These effects were reversed when cells were treated with the estrogen antagonist ICI182780, suggesting that genistein’s effects were mediated by ERs 109 .…”

Section: The Anti-diabetic Actions Of Genisteinmentioning

confidence: 98%

Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function

2013

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Type 2 diabetes is a result of chronic insulin resistance and loss of functional pancreatic β-cell mass. Strategies to preserve β-cell mass and a greater understanding of the mechanisms underlying β-cell turnover are needed to prevent and treat this devastating disease. Genistein, a naturally-occurring soy isoflavone, is reported to have numerous health benefits attributed to multiple biological functions. Over the past 10 years, numerous studies have demonstrated that genistein has anti-diabetic effects, in particular, direct effects on β-cell proliferation, glucose-stimulated insulin secretion and protection against apoptosis, independent of its functions as an estrogen receptor agonist, antioxidant, or tyrosine kinase inhibitor. Effects are structure-specific and not common to all flavonoids. While there are limited data on the effects of genistein consumption in humans with diabetes, there are a plethora of animal and cell-culture studies that demonstrate, at physiologically-relevant concentrations (<10 µM), a direct effect of genistein on β-cells. The effects appear to involve cAMP/PKA signaling and there are some studies that suggest an effect on epigenetic regulation of gene expression. This review focuses on the anti-diabetic effects of genistein in both in-vitro and in-vivo models and potential mechanisms underlying its direct effects on β-cells.

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Section: The Anti-diabetic Actions Of Genisteinmentioning

confidence: 98%

Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function

2013

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“…Genistein exerts a hypoglycemic effect in streptozocin‐diabetic rats and has been shown to improve islet β‐cell proliferation, survival, and mass via its effect on cAMP/PKA signaling and phosphorylation of extracellular signal‐related kinase (ERK)1/2 in human islets . Moreover, genistein reverses the damage to human pancreatic β cells caused by high glucose concentrations, suggesting a protective effect on these cells . Yang et al .…”

Section: Metabolic Syndrome and Genisteinmentioning

confidence: 99%

“…68,69 Moreover, genistein reverses the damage to human pancreatic b cells caused by high glucose concentrations, suggesting a protective effect on these cells. 70 Yang et al 71 demonstrated that genistein treatment significantly decreased hyperglycemia and islet cell loss in diabetic rats in a dose-dependent manner. Therefore, genistein seems to possess antidiabetic potential via its effects on islet cell preservation and improvement in glycemic control ( Figure 2).…”

Section: Effect Of Genistein On Diabetes and Risk Of Cancermentioning

confidence: 99%

Pleiotropic effects of genistein in metabolic, inflammatory, and malignant diseases

2013

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Genistein is a soy-derived biologically active isoflavone that exhibits diverse health-promoting effects. An increasing body of evidence shows that genistein influences lipid homeostasis and insulin resistance, counteracts inflammatory cytokines, and possesses antidiabetic properties. Genistein also impedes cancer progression by promoting apoptosis, inducing cell cycle arrest, modulating intracellular signaling pathways, and inhibiting angiogenesis and metastasis of neoplastic cells. This review summarizes the pleiotropic functions of genistein in common health disorders such as metabolic syndrome, chronic inflammatory diseases, and cancer. In the current era of uncontrolled health expenditure, a focus on the clinical development of nutritional agents with the capacity to prevent a variety of common health disorders is needed. As a micronutrient that exerts multifaceted effects ranging from antidiabetic to anticarcinogenic functions, genistein should be clinically developed further for use in the prevention and treatment of a variety of health disorders.

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“…In addition to these beneficial effects, genistein was found to protect pancreatic β cells from high glucose-induced apoptosis (72). In contrast, bafilomycin A1 reduced pancreatic islet size and impaired glucose tolerance in animal models (73,74) hypothetically linking this bacterial toxin to the development of type I diabetes (75).…”

Section: Discussionmentioning

confidence: 99%

The (pro)renin receptor mediates constitutive PLZF-independent pro-proliferative effects which are inhibited by bafilomycin but not genistein

Kirsch

Schrezenmeier

Klare

et al. 2014

International Journal of Molecular Medicine

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The (pro)renin receptor [(P)RR] is crucial for cardio-renal pathophysiology. The distinct molecular mechanisms of this receptor are still incompletely understood. The (P)RR is able to interact with different signalling proteins such as promyelocytic leukemia zinc finger protein (PLZF) and Wnt receptors. Moreover, domains of the (P)RR are essential for V-ATPase activity. V-ATPase- and Wnt-mediated effects imply constitutive, i.e., (pro)renin-independent functions of the (P)RR. Regarding ligand-dependent (P)RR signalling, the role of prorenin glycosylation is currently unknown. Therefore, the aim of this study was to analyse the contribution of constitutive (P)RR activity to its cellular effects and the relevance of prorenin glycosylation on its ligand activity. We were able to demonstrate that high glucose induces (P)RR signal transduction whereas deglycosylation of prorenin abolishes its intrinsic activity in neuronal and epithelial cells. By using siRNA against (P)RR or PLZF as well as the PLZF translocation blocker genistein and the specific V-ATPase inhibitor bafilomycin, we were able to dissect three distinct sub-pathways downstream of the (P)RR. The V-ATPase function is ligand-independently associated with strong pro-proliferative effects whereas prorenin causes moderate proliferation in vitro. In contrast, PLZF per se [i.e., in the absence of (pro)renin] does not interfere with cell number.

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Mechanisms of Genistein Protection on Pancreas Cell Damage in High Glucose Condition

Cited by 13 publications

References 25 publications

Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function

Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function

Pleiotropic effects of genistein in metabolic, inflammatory, and malignant diseases

The (pro)renin receptor mediates constitutive PLZF-independent pro-proliferative effects which are inhibited by bafilomycin but not genistein

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