Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats

doi:10.1016/j.taap.2012.11.015

	Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats
	Yu, Yunli 1,2; Wang, Xinting 1; Liu, Can 1; Yao, Dan 1,3; Hu, Mengyue 1; Li, Jia1 ; Hu, Nan 1; Liu, Li 1; Liu, Xiaodong 1
刊名	TOXICOLOGY AND APPLIED PHARMACOLOGY
	2013-02-01
卷号	266 期号:3 页码:375-384
关键词	Gatifloxacin Hyperglycemia Glucagon-like peptide 1 Insulin Diabetes
ISSN号	0041-008X
DOI	10.1016/j.taap.2012.11.015
文献子类	Article
英文摘要	Accumulating evidences have showed that gatifloxacin causes dysglycemia in both diabetic and non-diabetic patients. Our preliminary study demonstrated that gatifloxacin stimulated glucagon-like peptide 1 (GLP-1) secretion from intestinal cells. The aim of the study was to investigate the association between gatifloxacin-stimulated GLP-1 release and dysglycemia in both normal and streptozotocin-induced diabetic rats and explore the possible mechanisms. Oral administration of gatifloxacin (100 mg/kg/day and 200 mg/kg/day) for 3 and 12 days led to marked elevation of GLP-1 levels, accompanied by significant decrease in insulin levels and increase in plasma glucose. Similar results were found in normal rats treated with 3-day gatifloxacin. Gatifloxacin-stimulated GLP-1 release was further confirmed in NCI-H716 cells, which was abolished by diazoxide, a K-ATP channel opener. QT-PCR analysis showed that gatifloxacin also upregulated expression of proglucagon and prohormone convertase 3 mRNA. To clarify the contradiction on elevated GLP-1 without insulinotropic effect, effects of GLP-1 and gatifloxacin on insulin release were investigated using INS-1 cells. We found that short exposure (2 h) to GLP-1 stimulated insulin secretion and biosynthesis, whereas long exposure (24 h and 48 h) to high level of GLP-1 inhibited insulin secretion and biosynthesis. Moreover, we also confirmed gatifloxacin acutely stimulated insulin secretion while chronically inhibited insulin biosynthesis. All the results gave an inference that gatifloxacin stimulated over-secretion of GLP-1, in turn, high levels of GLP-1 and gatifloxacin synergistically impaired insulin release, worsening hyperglycemia. (C) 2012 Elsevier Inc. All rights reserved.
资助项目	National Science foundation of China[30873123] ; National Science foundation of China[81072693] ; National Science foundation of China[81102503] ; National Science foundation of China[81273587]
WOS关键词	GLUCOSE-HOMEOSTASIS ; DIABETIC-RATS ; IN-VITRO ; CELLS ; FLUOROQUINOLONES ; EXPRESSION ; ISLET ; POLYPEPTIDE ; THERAPY ; RELEASE
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000314329000006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277752]
专题	中国科学院上海药物研究所
通讯作者	Liu, Li
作者单位	1.China Pharmaceut Univ, Key Lab Drug Metab & Pharmacokinet, Nanjing 210009, Jiangsu, Peoples R China; 2.Soochow Univ, Dept Pharmaceut, Affiliated Hosp 2, Suzhou 215004, Peoples R China; 3.Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Yu, Yunli,Wang, Xinting,Liu, Can,et al. Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2013,266(3):375-384.
APA	Yu, Yunli.,Wang, Xinting.,Liu, Can.,Yao, Dan.,Hu, Mengyue.,...&Liu, Xiaodong.(2013).Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats.TOXICOLOGY AND APPLIED PHARMACOLOGY,266(3),375-384.
MLA	Yu, Yunli,et al."Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats".TOXICOLOGY AND APPLIED PHARMACOLOGY 266.3(2013):375-384.