Mangiferin, a xanthonoid found in plants including mangoes and iris unguicularis, was suggested in previous studies to have anti-hyperglycemic function, though the underlying mechanisms are largely unknown. This study was designed to determine the therapeutic effect of mangiferin by the regeneration of β-cells in mice following 70% partial pancreatectomy (PPx), and to explore the mechanisms of mangiferin-induced β-cell proliferation. For this purpose, adult C57BL/6J mice after 7–14 days post-PPx, or a sham operation were subjected to mangiferin (30 and 90 mg/kg body weight) or control solvent injection. Mangiferin-treated mice exhibited an improved glycemia and glucose tolerance, increased serum insulin levels, enhanced β-cell hyperplasia, elevated β-cell proliferation and reduced β-cell apoptosis. Further dissection at the molecular level showed several key regulators of cell cycle, such as cyclin D1, D2 and cyclin-dependent kinase 4 (Cdk4) were significantly up-regulated in mangiferin-treated mice. In addition, critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (PDX-1), neurogenin 3 (Ngn3), glucose transporter 2 (GLUT-2), Forkhead box protein O1 (Foxo-1), and glucokinase (GCK), were found to be promoted by mangiferin at both the mRNA and protein expression level. Thus, mangiferin administration markedly facilitates β-cell proliferation and islet regeneration, likely by regulating essential genes in the cell cycle and the process of islet regeneration. These effects therefore suggest that mangiferin bears a therapeutic potential in preventing and/or treating the diabetes.

Glaucoma is the leading cause of irreversible blindness worldwide and there is no effective treatment thus far. The trabecular meshwork has been identified as the major pathological area involved. Certain signaling pathways in the trabecular meshwork, including the Wnt, lysophosphatidic acid and transforming growth factor-β pathways, have been identified as novel therapeutic targets in glaucoma treatment. Meanwhile, it has been reported that key proteins in these pathways, particularly the primary transcription regulator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), exhibit interactions with the Hippo pathway. The Hippo pathway, which was first identified in Drosophila, has drawn great focus with regard to various aspects of studies in recent years. One role of the Hippo pathway in the regulation of organ size was indicated by more recent evidence. Defining the relevant physiological function of the Hippo pathway has proven to be extremely complicated. Studies have ascribed a role for the Hippo pathway in an overwhelming number of processes, including cell proliferation, cell death and cell differentiation. Therefore, the present review aimed to unravel the roles of YAP and TAZ in the Hippo pathway and the pathogenesis of glaucoma. Furthermore, a new and creative study for the treatment of glaucoma is provided.

This study was designed to determine the therapeutic effect of Agaricus bisporus lectins (ABL) by the regeneration of β-cells in mice following 70% partial pancreatectomy (PPx), and to explore the mechanisms of ABL-induced β-cell proliferation. Adult C57BL/6J mice were subjected to a 70% PPx operation or a sham operation, and mice received 10 mg/kg body weight of ABL or saline immediately after surgery. Blood glucose concentrations and insulin secretion levels were measured. To determine the growth rates of β-cells and duct cells, immunohistological analysis of pancreatic tissues was performed. Key cell cycle proteins and β-cell specific genes were measured by realtime polymerase chain reaction, Western blotting and immunohistological staining. In this study, a significant decrease in blood glucose concentrations, increase in glucose tolerance and expanded β-cell mass were observed in the ABL-treated mice. At the same time, after ABL treatment, increased β-cell proliferation rates were observed. Further studies on the expression of cyclin D1, cyclin D2 and Cdk4 demonstrated that these genes were significantly up-regulated in the ABL-treated mice. Meanwhile, Cdk4 activity was also enhanced. Moreover, the expression of PDX-1 (pancreatic and duodenal homeobox 1), Ngn3 (neurogenin 3), insulin, GLUT-1 (glucose transporter 1) and glucokinase was also increased in the ABL-treated mice. These findings demonstrate that ABL administration could partially reverse the impaired β-cell growth potential by regulating cell cycle proteins. Induction of islet β-cell proliferation by ABL suggests the therapeutic potential in preventing and/or treating diabetes.

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