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1.
World J Diabetes ; 14(11): 1643-1658, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-38077805

ABSTRACT

BACKGROUND: Impaired glucose tolerance (IGT) is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes. When IGT occurs, insulin sensitivity decreases, causing a reduction in insulin secretion and an increase in glucagon secretion. Recently, vascular endothelial growth factor B (VEGFB) has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity. Therefore, we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion, thus contributing to the prevention and cure of prediabetes. AIM: To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT. METHODS: We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression. Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay, and the protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) was determined using western blot. Further, mRNA expression of forkhead box protein O1, phosphoenolpyruvate carboxykinase, and glucose-6 phosphatase was detected via quantitative polymerase chain reaction, and the correlation between the expression of proteins was analyzed via bioinformatics. RESULTS: In mice with IGT and VEGFB knockout, glucagon secretion increased, and the protein expression of PI3K/AKT decreased dramatically. Further, in mice with VEGFB overexpression, glucagon levels declined, with the activation of the PI3K/AKT signaling pathway. CONCLUSION: VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

2.
Bioorg Med Chem ; 27(15): 3469-3476, 2019 08 01.
Article in English | MEDLINE | ID: mdl-31253536

ABSTRACT

The first and in-depth chemical investigation of the South China Sea soft coral Sinularia scabra has resulted to the isolation of a library of diverse cembrane type diterpenoids, including six new compounds, namely xiguscabrates A and B (1 and 2), xiguscabral A (3), xiguscabrols A and B (4 and 5), and 8-epi-xiguscabrol B (6), and twenty-seven known analogs (7-33). Their structures were elucidated by extensive spectroscopic analysis and by the comparison with literature data. In bioassay, several isolates exhibited inhibitory effects on the ConA-induced T lymphocytes and/or LPS-induced B lymphocytes proliferation. Among them, compound 24 showed considerable specific inhibition on B cell proliferation, with IC50 value of 4.4 µM and selectivity index (SI) of 10.9. The structure-activity relationship (SAR) of the tested metabolites was analyzed, and the further mechanism study of the specific B-cell targeted immunosuppressive compound 24 on purified CD19+ B cells was also performed to uncover the effects on the function and maturity of B cells, including cytokines production, abnormal activation, antigen presenting capacity and plasma cells formation.


Subject(s)
Anthozoa/chemistry , B-Lymphocytes/drug effects , Diterpenes/pharmacology , Immunosuppressive Agents/pharmacology , T-Lymphocytes/drug effects , Animals , B-Lymphocytes/immunology , Cell Proliferation/drug effects , Concanavalin A/antagonists & inhibitors , Concanavalin A/pharmacology , Cytokines/antagonists & inhibitors , Cytokines/biosynthesis , Cytokines/immunology , Diterpenes/chemistry , Diterpenes/isolation & purification , Dose-Response Relationship, Drug , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/isolation & purification , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Molecular Structure , Structure-Activity Relationship , T-Lymphocytes/immunology
3.
J Asian Nat Prod Res ; 17(2): 199-216, 2015.
Article in English | MEDLINE | ID: mdl-25559315

ABSTRACT

Marine natural products constitute a huge reservoir of anticancer agents. Consequently during the past decades, several marine anticancer compounds have been isolated, identified, and approved for anticancer treatment or are under trials. In this article the sources, structure, bioactivities, mode of actions, and analogs of some promising marine and derived anticancer compounds have been discussed.


Subject(s)
Antineoplastic Agents , Biological Products , Marine Biology , Molecular Structure
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