title: BBT improves glucose homeostasis by ameliorating β-cell dysfunction in type 2 diabetic mice.
abstract: 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 Ca(2) (+) 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.
authors.affiliation: Key Laboratory of Receptor ResearchShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, ChinaCollege of Life and Environmental SciencesShanghai Normal University, 100 Guilin Road, Shanghai 200234, ChinaDepartment of PharmacologyChina Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Xin-gang
authors.initials: XG
authors.lastname: Yao
authors.affiliation: Key Laboratory of Receptor ResearchShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, ChinaCollege of Life and Environmental SciencesShanghai Normal University, 100 Guilin Road, Shanghai 200234, ChinaDepartment of PharmacologyChina Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Receptor ResearchShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, ChinaCollege of Life and Environmental SciencesShanghai Normal University, 100 Guilin Road, Shanghai 200234, ChinaDepartment of PharmacologyChina Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Gai-hong
authors.initials: GH
authors.lastname: Wang
authors.affiliation: Key Laboratory of Receptor ResearchShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, ChinaCollege of Life and Environmental SciencesShanghai Normal University, 100 Guilin Road, Shanghai 200234, ChinaDepartment of PharmacologyChina Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Lei
authors.affiliation: Key Laboratory of Receptor ResearchShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, ChinaCollege of Life and Environmental SciencesShanghai Normal University, 100 Guilin Road, Shanghai 200234, ChinaDepartment of PharmacologyChina Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Quan
authors.affiliation: Key Laboratory of Receptor ResearchShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, ChinaCollege of Life and Environmental SciencesShanghai Normal University, 100 Guilin Road, Shanghai 200234, ChinaDepartment of PharmacologyChina Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Yan-hua
authors.initials: YH
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Receptor ResearchShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, ChinaCollege of Life and Environmental SciencesShanghai Normal University, 100 Guilin Road, Shanghai 200234, ChinaDepartment of PharmacologyChina Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wan
authors.affiliation: Key Laboratory of Receptor ResearchShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, ChinaCollege of Life and Environmental SciencesShanghai Normal University, 100 Guilin Road, Shanghai 200234, ChinaDepartment of PharmacologyChina Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Jin-pei
authors.initials: JP
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Receptor ResearchShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, ChinaCollege of Life and Environmental SciencesShanghai Normal University, 100 Guilin Road, Shanghai 200234, ChinaDepartment of PharmacologyChina Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China xshen@simm.ac.cn lhhu@simm.ac.cn jingchen@simm.ac.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Receptor ResearchShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, ChinaCollege of Life and Environmental SciencesShanghai Normal University, 100 Guilin Road, Shanghai 200234, ChinaDepartment of PharmacologyChina Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China xshen@simm.ac.cn lhhu@simm.ac.cn jingchen@simm.ac.cn.
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Hu
authors.affiliation: Key Laboratory of Receptor ResearchShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, ChinaCollege of Life and Environmental SciencesShanghai Normal University, 100 Guilin Road, Shanghai 200234, ChinaDepartment of PharmacologyChina Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China xshen@simm.ac.cn lhhu@simm.ac.cn jingchen@simm.ac.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D059305:Diet, High-Fat; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000378:metabolism*; D057809:HEK293 Cells; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; C000597010:N-(2-benzoylphenyl)-5-bromo-2-thiophenecarboxamide; D013876:Thiophenes; D013311:Streptozocin; D005947:Glucose
keywords: glucose homeostasis; glucose-stimulated insulin secretion (GSIS); β-cell death; β-cell dysfunction