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  • Author: Lihong Hu x
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Yang Zhang, Weimin Zhang, Huiyi Yang, Wenliang Zhou, Chaoqun Hu and Lihong Zhang

Previously, the ricefield eel (Monopterus albus) was speculated to have only one cytochrome p450 aromatase gene. In this study, however, the cDNAs encoding two distinct cytochrome p450 aromatases, cyp19a1a and cyp19a1b, were isolated. The genomic organizations of both cyp19 genes were conserved when compared with other teleosts. Northern blot detected an abundant expression of cyp19a1a in the ovary, and cyp19a1b in the hypothalamus. RT-PCR coupled with Southern blot showed that cyp19a1a was expressed predominantly in the gonads of both sexes, with higher levels in the ovary than testis, while cyp19a1b was expressed in all the tissues examined in the male, but only in the brain and pituitary in the female. The levels of cyp19a1a mRNA in the ovary were increased significantly during vitellogenesis, but decreased significantly at mature stage. The levels of cyp19a1b mRNA in the brain and pituitary did not vary significantly during vitellogenesis. As ovarian development shifted from vitellogenesis to maturation, the levels of cyp19a1b mRNA was decreased significantly in the brain, but increased significantly in the pituitary. During natural sex change from female to male, the levels of cyp19a1a mRNA in the gonad were significantly decreased. The levels of cyp19a1b mRNA in the hypothalamus were significantly increased at the early intersexual phase, whereas the expression levels in the pituitary were significantly decreased at the intersexual phases. Taken together, these results showed a novel sexual dimorphism of cyp19a1b mRNA tissue distribution, and both CYP19 genes were associated with the ovarian development and natural sex change of the ricefield eel.

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Te Du, Liu Yang, Xu Xu, Xiaofan Shi, Xin Xu, Jian Lu, Jianlu Lv, Xi Huang, Jing Chen, Heyao Wang, Ji-Ming Ye, Lihong Hu and Xu Shen

Vincamine, a monoterpenoid indole alkaloid extracted from madagascar periwinkle, is clinically used for the treatment of cardio-cerebrovascular diseases, while also treated as a dietary supplement with nootropic function. Given the neuronal protection of vincamine and the potency of β-cell amelioration in treating type 2 diabetes mellitus (T2DM), we investigated the potential of vincamine in protecting β-cells and ameliorating glucose homeostasis in vitro and in vivo. Interestingly, we found that vincamine could protect INS-832/13 cells function by regulating G-protein-coupled receptor 40 (GPR40)/cAMP/Ca2+/IRS2/PI3K/Akt signaling pathway, while increase glucose-stimulated insulin secretion (GSIS) via modulating GPR40/cAMP/Ca2+/CaMKII pathway, which reveals a novel mechanism underlying GPR40-mediated cell protection and GSIS in INS-832/13 cells. Moreover, administration of vincamine effectively ameliorated glucose homeostasis in either HFD/STZ or db/db type 2 diabetic mice. To our knowledge, our current work might be the first report on vincamine targeting GPR40 and its potential in the treatment of T2DM.

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Xin-gang Yao, Xin Xu, Gai-hong Wang, Min Lei, Ling-ling Quan, Yan-hua Cheng, Ping Wan, Jin-pei Zhou, Jing Chen, Li-hong Hu and Xu Shen

Impaired glucose-stimulated insulin secretion (GSIS) and increasing β-cell death are two typical dysfunctions of pancreatic β-cells in individuals that are destined to develop type 2 diabetes, and improvement of β-cell function through GSIS enhancement and/or inhibition of β-cell death is a promising strategy for anti-diabetic therapy. In this study, we discovered that the small molecule, N-(2-benzoylphenyl)-5-bromo-2-thiophenecarboxamide (BBT), was effective in both potentiating GSIS and protecting β-cells from cytokine- or streptozotocin (STZ)-induced cell death. Results of further studies revealed that cAMP/PKA and long-lasting (L-type) voltage-dependent Ca2 + channel/CaMK2 pathways were involved in the action of BBT against GSIS, and that the cAMP/PKA pathway was essential for the protective action of BBT on β-cells. An assay using the model of type 2 diabetic mice induced by high-fat diet combined with STZ (STZ/HFD) demonstrated that BBT administration efficiently restored β-cell functions as indicated by the increased plasma insulin level and decrease in the β-cell loss induced by STZ/HFD. Moreover, the results indicated that BBT treatment decreased fasting blood glucose and HbA1c and improved oral glucose tolerance further highlighting the potential of BBT in anti-hyperglycemia research.

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Te Du, Liu Yang, Xu Xu, Xiaofan Shi, Xin Xu, Jian Lu, Jianlu Lv, Xi Huang, Jing Chen, Heyao Wang, Jiming Ye, Lihong Hu and Xu Shen

Vincamine, a monoterpenoid indole alkaloid extracted from the Madagascar periwinkle, is clinically used for the treatment of cardio-cerebrovascular diseases, while also treated as a dietary supplement with nootropic function. Given the neuronal protection of vincamine and the potency of β-cell amelioration in treating type 2 diabetes mellitus (T2DM), we investigated the potential of vincamine in protecting β-cells and ameliorating glucose homeostasis in vitro and in vivo. Interestingly, we found that vincamine could protect INS-832/13 cells function by regulating G-protein-coupled receptor 40 (GPR40)/cAMP/Ca2+/IRS2/PI3K/Akt signaling pathway, while increasing glucose-stimulated insulin secretion (GSIS) by modulating GPR40/cAMP/Ca2+/CaMKII pathway, which reveals a novel mechanism underlying GPR40-mediated cell protection and GSIS in INS-832/13 cells. Moreover, administration of vincamine effectively ameliorated glucose homeostasis in either HFD/STZ or db/db type 2 diabetic mice. To our knowledge, our current work might be the first report on vincamine targeting GPR40 and its potential in the treatment of T2DM.