BBT improves glucose homeostasis by ameliorating beta-cell dysfunction in type 2 diabetic mice

doi:10.1530/JOE-14-0721

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	BBT improves glucose homeostasis by ameliorating beta-cell dysfunction in type 2 diabetic mice
	Yao, Xin-gang 3; Xu, Xin 3; Wang, Gai-hong 3; Lei, Min3 ; Quan, Ling-ling 2; Cheng, Yan-hua 1; Wan, Ping 2; Zhou, Jin-pei 1; Chen, Jing3 ; Hu, Li-hong 3
刊名	JOURNAL OF ENDOCRINOLOGY
	2015-03
卷号	224 期号:3 页码:327-341
关键词	beta-cell dysfunction glucose-stimulated insulin secretion (GSIS) beta-cell death glucose homeostasis Journal of Endocrinology
ISSN号	0022-0795
DOI	10.1530/JOE-14-0721
文献子类	Article
英文摘要	Impaired glucose-stimulated insulin secretion (GSIS) and increasing beta-cell death are two typical dysfunctions of pancreatic beta-cells in individuals that are destined to develop type 2 diabetes, and improvement of beta-cell function through GSIS enhancement and/or inhibition of beta-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 beta-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 beta-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 beta-cell functions as indicated by the increased plasma insulin level and decrease in the beta-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.
资助项目	National Natural Science Foundation of China[81373461] ; National Natural Science Foundation of China[81473141] ; National Natural Science Foundation of China[91413102] ; National Natural Science Foundation of China[81220108025] ; National Natural Science Foundation of China[91213306]
WOS关键词	DEPENDENT PROTEIN-KINASE ; GLUCAGON-LIKE PEPTIDE-1 ; STIMULATED INSULIN-SECRETION ; INCRETIN-BASED THERAPIES ; ACID-INDUCED APOPTOSIS ; REGULATED KINASES ; RAT PANCREAS ; CA2+ INFLUX ; B-CELLS ; INHIBITORS
WOS研究方向	Endocrinology & Metabolism
语种	英语
出版者	BIOSCIENTIFICA LTD
WOS记录号	WOS:000349562500016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276632]
专题	药物安全性评价中心药理学第三研究室
通讯作者	Shen, Xu
作者单位	1.China Pharmaceut Univ, Dept Pharmacol, Nanjing 210009, Jiangsu, Peoples R China 2.Shanghai Normal Univ, Coll Life & Environm Sci, Shanghai 200234, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Yao, Xin-gang,Xu, Xin,Wang, Gai-hong,et al. BBT improves glucose homeostasis by ameliorating beta-cell dysfunction in type 2 diabetic mice[J]. JOURNAL OF ENDOCRINOLOGY,2015,224(3):327-341.
APA	Yao, Xin-gang.,Xu, Xin.,Wang, Gai-hong.,Lei, Min.,Quan, Ling-ling.,...&Shen, Xu.(2015).BBT improves glucose homeostasis by ameliorating beta-cell dysfunction in type 2 diabetic mice.JOURNAL OF ENDOCRINOLOGY,224(3),327-341.
MLA	Yao, Xin-gang,et al."BBT improves glucose homeostasis by ameliorating beta-cell dysfunction in type 2 diabetic mice".JOURNAL OF ENDOCRINOLOGY 224.3(2015):327-341.