期刊文献+
共找到318篇文章
< 1 2 16 >
每页显示 20 50 100
Ghrelin regulates insulin resistance by targeting insulin-like growth factor-1 receptor via miR-455-5p in hepatic cells
1
作者 GUO Zhan-hong JU Yue-jun +4 位作者 SHEN Ting ZHANG Lin-qi SHENG Zhong-qi WU Run-ze KONG Ying-hong 《Journal of Hainan Medical University》 CAS 2024年第1期22-28,共7页
Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption,... Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption, intracellular glycogen content, phosphorylation of PI3K and Akt stimulated by insulin, expression of miR-455-5p, as well as IGF-1R protein level were analyzed. In addition, bioinformatic analysis, dual luciferase reporter assay, miR- 455-5p mimic or inhibitor treatment was conducted to investigate the molecular mechanisms. Results: High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content. DAG reversed the effect of high glucose on glucose metabolism, increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin, as well as downregulated miR-455-5p expression. Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p. Dual luciferase reporter assay, as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p. Conclusion: DAG improves insulin resistance via miR-455-5p- mediated activation of IGF-1R/PI3K/Akt system, suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy. 展开更多
关键词 GHRELIN miR-455-5p IGF-1R insulin resistance HepG2 cells
下载PDF
Neurotransmitters regulateβcells insulin secretion:A neglected factor 被引量:1
2
作者 Chu-Chu Kong Ji-Dong Cheng Wei Wang 《World Journal of Clinical Cases》 SCIE 2023年第28期6670-6679,共10页
βcells are the main cells responsible for the hypoglycemic function of pancreatic islets,and the insulin secreted by these cells is the only hormone that lowers blood glucose levels in the human body.βcells are regu... βcells are the main cells responsible for the hypoglycemic function of pancreatic islets,and the insulin secreted by these cells is the only hormone that lowers blood glucose levels in the human body.βcells are regulated by various factors,among which neurotransmitters make an important contribution.This paper discusses the effects of neurotransmitters secreted by various sympathetic and parasympathetic nerves onβcells and summarizes the mechanisms by which various neurotransmitters regulate insulin secretion.Many neurotransmitters do not have a single source and are not only released from nerve terminals but also synthesized byβcells themselves,allowing them to synergistically regulate insulin secretion.Almost all of these neurotransmitters depend on the presence of glucose to function,and their actions are mostly related to the Ca^(2+)and cAMP concentrations.Although neurotransmitters have been extensively studied,many of their mechanisms remain unclear and require further exploration by researchers. 展开更多
关键词 βcells insulin secretion NEUROLOGY Type 2 diabetes ISLET
下载PDF
Anti-diabetic effects of Caulerpa lentillifera:stimulation of insulin secretion in pancreatic β-cells and enhancement of glucose uptake in adipocytes 被引量:13
3
作者 Bhesh Raj Sharma Dong Young Rhyu 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2014年第7期575-580,共6页
Objective:To evaluate anti-diabetic effect of Caulrpa kntillifera(C.lentillifera).Methods:The inhibitory effect of C.lentillifera extract on dipeptidyl peptidase-IV and a-glucosidase enzyme was measured in a cell free... Objective:To evaluate anti-diabetic effect of Caulrpa kntillifera(C.lentillifera).Methods:The inhibitory effect of C.lentillifera extract on dipeptidyl peptidase-IV and a-glucosidase enzyme was measured in a cell free system.Then,interleukin-1βand interferon-γinduced cell death and insulin secretion were measured in rat insulinoma(RIN)cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ELISA kit,respectively.Glucose uptake and glucose transporter expression were measured by fluorometry and western blotting,using 3T3-Ll adipocytes.Results:C.lentillifera extract significantly decreased dipeptidyl peptidase-IV and a-glucosidase enzyme activities,and effectively inhibited cell death and iNOS expression in interleukin-1βand interfcron-γinduced RIK cells.Furthermore,C.lntillifera extract significantly enhanced insulin secretion in RTN cells and glucose transporter expression and glucose uptake in 3T3-L1adipocytes.Conclusions:Thus,our results suggest that C.lentillifera could be used as a potential antidiabetic agenl. 展开更多
关键词 Gaulerpa lentillifera Diabetes Glucose uptake insulin secretION RIN cells 3T3-1 1 ADIPOCYTES
下载PDF
Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca2+ and cyclic adenosine monophosphate levels through PI3K/AKT pathway 被引量:1
4
作者 Jing-Dan Jia Wen-Guo Jiang +4 位作者 Xu Luo Rong-Rong Li Yu-Chi Zhao Geng Tian Ya-Na Li 《World Journal of Diabetes》 SCIE 2021年第4期480-498,共19页
BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism... BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D. 展开更多
关键词 Type 2 diabetes insulin secretion MIN6 cells Vascular endothelial growth factor B Blood glucose regulation
下载PDF
Types of voltage-dependent calcium channels involved in high potassium depolarization-induced amylase secretion in the exocrine pancreatic tumour cell line AR4-2J 被引量:1
5
作者 CUI ZONG JIE (Beijing Agricultural University Faculty of Biological Sciences Beijing 100094, China) 《Cell Research》 SCIE CAS CSCD 1998年第1期23-31,共9页
In the perifused fura-2 loaded exocrine pancreatic acinar cell line AR4-2J pulses of high potassium induced repetitive increases in intracellular calcium. Attached cells when stimulated with high potassium secreted la... In the perifused fura-2 loaded exocrine pancreatic acinar cell line AR4-2J pulses of high potassium induced repetitive increases in intracellular calcium. Attached cells when stimulated with high potassium secreted large amount of amylase. High potassium-induced secretion was dependent both on the concentration of potassium and duration of stimulation. High potassium induced increases in intracellular calcium were inhibited by voltage-dependent calcium channel antagonists with an order of potency as follows: nifedipine > ω-agatoxin IVA > ω-conotoxin GVIA. In contrast, the L-type calcium channel antagonist nifedipine almost completely inhibited potassium-induced amylase secretion, whereas the N-type channel antagonist ω-conotoxin GVIA was without effect. The P-type channel antagonist ω-agatoxin IVA had a small inhibitory effect, but this inhibition was not significant at the level of amylase secretion. In conclusion, the AR4-2J cell line possesses different voltage-dependent calcium channels (L, P,N) with the L-type predominantly involved in depolarization induced amylase secretion. 展开更多
关键词 AR4-2J pancreatic acinar cells amylase secretion calcium channels
下载PDF
Caribbean maitotoxin elevates [Ca^(2+)]i and activates non-selective cation channels in HIT-T15 cells
6
作者 Xin-Zhong Lu Robert Deckey +2 位作者 Guo-Liang Jiao Hui-Feng Ren Ming Li 《World Journal of Diabetes》 SCIE CAS 2013年第3期70-75,共6页
AIM:To investigate the cytotoxic mechanism of caribbean maitotoxin(MTX-C) in mammalian cells.METHODS:We used whole-cell patch-clamp techniques and fluorescence calcium imaging to determine the cellular toxic mechanism... AIM:To investigate the cytotoxic mechanism of caribbean maitotoxin(MTX-C) in mammalian cells.METHODS:We used whole-cell patch-clamp techniques and fluorescence calcium imaging to determine the cellular toxic mechanisms of MTX-C in insulin secreting HIT-T15 cells,which is a system where the effects of MTX have been observed.HIT-T15 cells stably express L-type calcium current,making it a suitable model for this study.Using the fluorescence calcium indicator Indo-1 AM,we found that there is a profound increase in HIT-T15 intracellular free calcium 3 min after application of 200 nmol/L MTX-C.RESULTS:About 3 min after perfusion of MTX-C,a gradual increase in free calcium concentration was observed.This elevation was sustained throughout the entire recording period.Application of MTX-C did not elicit the L-type calcium current,but large cationiccurrents appeared after applying MTX-C to the extracellular solution.The current-voltage relationship of the cation current is approximately linear within the voltage range from-60 to 50 mV,but flattened at voltages at-80 and-100 mV.These results indicate that MTX-C induces a non-voltage activated,inward current under normal physiological conditions,which by itself or through a secondary mechanism results in a large amount of cationic influx.The biophysical mechanism of MTX-C is different to its isoform,pacific maitotoxin(MTX-P),when the extracellular calcium is removed.CONCLUSION:We conclude that MTX-C causes the opening of non-selective,non-voltage-activated ion channels,which elevates level of intracellular calcium concentration and leads to cellular toxicities. 展开更多
关键词 Maitotoxin Calcium fluorescence High voltage GATED Ca2+ channels WHOLE cell PATCH CLAMP insulin secreting cells
下载PDF
GLP-1、Betacellulin、Activin A、bFGF和Nicotinamide联合诱导小鼠胚胎干细胞分化为胰岛素分泌细胞 被引量:5
7
作者 吴木潮 陈黎红 +1 位作者 徐明彤 程桦 《中山大学学报(医学科学版)》 CAS CSCD 北大核心 2004年第5期426-430,共5页
【目的】探讨体外联合应用GLP-1、betacellulin、activinA、bFGF和nicotinamide5种生长因子能否将小鼠胚胎干细胞(ES细胞)诱导分化为胰岛素分泌细胞。【方法】以GLP-1、betacellulin、activinA、bFGF和nicoti-namide5种生长因子诱导E14.... 【目的】探讨体外联合应用GLP-1、betacellulin、activinA、bFGF和nicotinamide5种生长因子能否将小鼠胚胎干细胞(ES细胞)诱导分化为胰岛素分泌细胞。【方法】以GLP-1、betacellulin、activinA、bFGF和nicoti-namide5种生长因子诱导E14.1小鼠ES细胞30d后,应用RT-PCR、DTZ染色和免疫组化检测分化细胞胰岛素表达,以流式细胞仪检测胰岛素分泌细胞的分化率,用RIA法测定培养液中胰岛素水平。【结果】分化细胞可检测到胰岛素mRNA表达,DTZ染色和胰岛素免疫组化染色阳性,胰岛素分泌细胞的分化率平均为13.6%±3.7%,在5.6mmol/L和25mmol/L葡萄糖浓度作用下培养液中胰岛素水平分别为(0.04±0.01)ng/mL和(0.09±0.02)ng/mL。【结论】体外联合应用GLP-1、betacellulin、activinA、bFGF和nicotinamide5种生长因子能将小鼠ES细胞诱导分化为胰岛素分泌细胞,但胰岛素分泌功能较差。 展开更多
关键词 胰岛素分泌细胞 GLP-1 FGF 生长因子 胰岛素水平 干细胞分化 联合诱导 分化细胞 小鼠胚胎 ES细胞
下载PDF
β-cell dysfunction: Its critical role in prevention and management of type 2 diabetes 被引量:20
8
作者 Yoshifumi Saisho 《World Journal of Diabetes》 SCIE CAS 2015年第1期109-124,共16页
Type 2 diabetes(T2DM) is characterized by insulin resistance and β-cell dysfunction. Although, in contrast to type 1 diabetes, insulin resistance is assumed to be a major pathophysiological feature of T2 DM, T2 DM ne... Type 2 diabetes(T2DM) is characterized by insulin resistance and β-cell dysfunction. Although, in contrast to type 1 diabetes, insulin resistance is assumed to be a major pathophysiological feature of T2 DM, T2 DM never develops unless β-cells fail to compensate insulin resistance. Recent studies have revealed that a deficit of β-cell functional mass is an essential component of the pathophysiology of T2 DM, implying that β-cell deficit is a common feature of both type 1 and type 2 diabetes. β-cell dysfunction is present at the diagnosis of T2 DM and progressively worsens with disease duration. β-cell dysfunction is associated with worseningof glycemic control and treatment failure; thus, it is important to preserve or recover β-cell functional mass in the management of T2 DM. Since β-cell regenerative capacity appears somewhat limited in humans, reducing β-cell workload appears to be the most effective way to preserve β-cell functional mass to date, underpinning the importance of lifestyle modification and weight loss for the treatment and prevention of T2 DM. This review summarizes the current knowledge on β-cell functional mass in T2 DM and discusses the treatment strategy for T2 DM. 展开更多
关键词 β-cell insulin secretION Type 2 DIABETES PREVENTION Treatment
下载PDF
Advances and challenges in the differentiation of pluripotent stem cells into pancreatic β cells 被引量:2
9
作者 Essam M Abdelalim Mohamed M Emara 《World Journal of Stem Cells》 SCIE CAS 2015年第1期174-181,共8页
Pluripotent stem cells(PSCs) are able to differentiate into several cell types, including pancreatic β cells. Differentiation of pancreatic β cells depends on certain transcription factors, which function in a coord... Pluripotent stem cells(PSCs) are able to differentiate into several cell types, including pancreatic β cells. Differentiation of pancreatic β cells depends on certain transcription factors, which function in a coordinated way during pancreas development. The existing protocols for in vitro differentiation produce pancreatic β cells, which are not highly responsive to glucose stimulation except after their transplantation into immune-compromised mice and allowing several weeks for further differentiation to ensure the maturation of these cells in vivo. Thus, although the substantial improvement that has been made for the differentiation of induced PSCs and embryonic stem cells toward pancreatic β cells, several challenges still hindering their full generation. Here, we summarize recent advances in the differentiation of PSCs into pancreatic β cells and discuss the challenges facing their differentiation as well as the different applications of these potential PSC-derived β cells. 展开更多
关键词 EMBRYONIC stem cells Induced pluripotentstem cells insulin-secreting cells In VITRO In vivo DIFFERENTIATION MATURATION
下载PDF
SIRT5 protects pancreatic beta cell from glycolipotoxicity- induced apoptosis via interaction with BcI-XL
10
《中国药理学通报》 CAS CSCD 北大核心 2015年第B11期58-59,共2页
Progressive beta cell apoptosis is a major cause leading to a decline in beta cell mass in type 2 diabetes. While it has been discovered that mitochondrial protein Sirtuin 5 ( SIRT5 ) functions as the primary site o... Progressive beta cell apoptosis is a major cause leading to a decline in beta cell mass in type 2 diabetes. While it has been discovered that mitochondrial protein Sirtuin 5 ( SIRT5 ) functions as the primary site of oxidative metabolism and plays crucial roles in apoptosis and intracellular signaling, the contribution of SIRT5 in beta cell re- mains to be fully defined. Given the potential benefit of SIRT5 activation in cell metabolism, this study aimed to examine whether overexpression of SIRT5 in beta cells is sufficient to prevent saturated fatty acid induced impair- ment in insulin secretion and apoptosis, thus elucidating the role of SIRT5 in beta cell protection. In line with our previous study, two kinds of pancreatic beta cell lines were selected for the detection. Mouse-derived NIT-1 cells as well as human-derived PANC-1 cells were transfected with GFP-SIRT5-Ad plasmid and cell apoptosis was induced by palmitic acid (0.5 mM) , validated with TUNEL-DAPI double staining and RTCA iCelligence cell growth moni- tor system. Compared with control group, it was shown that SIRT5 overexpression could significantly reduce the quantity of apoptotic beta cells under chronic exposure to palmitic acid, accompanied with decreased Caspase 3 and Caspase 9 activities. Accordingly, cytochrome C oxidase activity in cells was also suppressed. Meanwhile, palmitic acid suppressed glucose-stimulated insulin secretion, but SIRT5 overexpression could recover the beta cell insulin secretion capacity against glucose fluctuation. Moreover, it is discovered that novel binding relationship exists be- tween SIRT5 and Bcl-XL, providing a reliable explanation for the anti-apoptosis role of SIRT5. Together, these re- sults reveal a potential role of SIRT5 in improvement of saturated fatty acid -induced beta cell dysfunction and apop- tosis. Considering the role of beta cell apoptosis in T2DM, overexpression or activation of SIRT5 may provide an e-rumpent approach as a potential target for beta cell protection. This approach might actually reverse the disease to a degree rather than just palliate glycemia. 展开更多
关键词 SIRT5 cell apoptosis BETA cell BCL-XL insulin secretION RTCA icelligence monitor system
下载PDF
<i>In Vivo</i>and <i>in Vitro</i>Evaluation of Anti Diabetic and Insulin Secretagogue Activities of <i>Capparis zeylanica</i>
11
作者 Umamahesh Balekari Ciddi Veeresham 《Pharmacology & Pharmacy》 2015年第7期311-320,共10页
Since ancient times, traditional medicines have been in the usage for the treatment of Diabetes mellitus. An edible fruit from traditional medicinal plant Capparis zeylanica (CZ) was studied for its anti diabetic, ins... Since ancient times, traditional medicines have been in the usage for the treatment of Diabetes mellitus. An edible fruit from traditional medicinal plant Capparis zeylanica (CZ) was studied for its anti diabetic, insulin secretagogue activities and mechanisms involved in it. In Streptozotocin induced diabetes rats, oral administration of Capparis zeylanica methanolic extract (CZME) (200 mg/kg body weight) for 28 days showed a significant reduction in blood glucose levels by 35.53% and enhanced circulating insulin levels by 81.82% than the diabetic control rats. The insulin secretagogue activity mechanisms of the extract were evaluated by using mouse insulinoma beta cell line (MIN6-β). The extract stimulated insulin release in dependent manner of glucose concentration (3 - 16.7 mM) and extract dose (5 - 500 μg/mL). The insulin releasing effect of the extract was significantly enhanced by 3-isobutyl-1-methyl xanthine, glibenclamide, elevated extracellular calcium and K+ depolarized media. This insulin release was significantly reduced in calcium blocking conditions (by nifedipine and EGTA), in the presence of potassium channel opener (diazoxide). Hence, anti diabetic activity of CZME might be a result of its stimulatory effect on insulin release from pancreatic beta cells via KATP channel dependent and independent ways. These results indicate that CZ fruits have the potential to use in diabetes therapy. 展开更多
关键词 ANTI DIABETIC insulin secretagogue MIN6-β cells KATP Channel
下载PDF
The impact of Hypoglycemic Ziyabiti Tablets (HZT) on diabetes mellitus rats and its activity in cultured rat liver cells
12
作者 李桂荣 FAN Yong +5 位作者 Moore N WANG Xiaofeng SHANG Jing LIU Jianzhong 王烨 李琳琳 《新疆医科大学学报》 CAS 2017年第12期1507-1512,共6页
Objective Hypoglycemic Ziyabiti Tablets(HZT)is a traditional multicomponent treatment for diabetes in Xinjiang Uyghur Traditional Medicine.The present study aimed to investigate the effect of HZT in diabetic rats and ... Objective Hypoglycemic Ziyabiti Tablets(HZT)is a traditional multicomponent treatment for diabetes in Xinjiang Uyghur Traditional Medicine.The present study aimed to investigate the effect of HZT in diabetic rats and its activity in cultured liver cells to investigate the relative mechanisms.Methods 10 days high-fat diet fed rats were intraperitoneally injected with alloxan(ALX)at next two subsequent days to induce diabetes mellitus(DM).Then were divided into 5 groups:saline,positive DM control and DM groups treated with different doses of HZT.Fasting blood glucose(FBG),total cholesterol(TC),total triglycerides(TG),high-density lipoprotein(HDL-C),fasting insulin(FI),insulin secretion(IS)and insulin sensitivity index(ISI)were measured.The IC_(50) of HZT in L-02 cells was determined by MTT assay,in intact and in paracetamol-induced liver injury(Par),on lactate dehydrogenase(LDH)activity and on glucose consumption.Results HZT decreased FBG and TC(P <0.05),increased IS(P <0.05)and at 440 mg·kg^(-1)·d^(-1) increased FI(P < 0.01).In vitro,HZT at 0.1,0.2,and 0.4 mg/mL decreased LDH activity and promoted glucose consumption.Conclusion The hypoglycemic mechanism of HZT is possibly related to increased insulin secretion from the pancreas and increased utilization of glucose by the liver. 展开更多
关键词 中药复方 链脲佐菌素 糖尿病 血糖
下载PDF
Forkhead box O1 / pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E-2-induced pancreatic beta-cell dysfunction
13
作者 Meng, Zhuoxian Lv, Jinghuan +6 位作者 Luo, Ying Lin, Yan Zhu, Yunxia Nie, Jia Yang, Tao Sun, Yujie Han, Xiao 《南京医科大学学报(自然科学版)》 CAS CSCD 北大核心 2010年第1期45-45,共1页
Prostaglandin E-2(PGE(2)) is a well-known mediator of beta-cell dysfunction in both type 1 and type 2 diabetes.We recently reported that down-regulation of the Akt pathway activity is implicated in PGE(2)-induced panc... Prostaglandin E-2(PGE(2)) is a well-known mediator of beta-cell dysfunction in both type 1 and type 2 diabetes.We recently reported that down-regulation of the Akt pathway activity is implicated in PGE(2)-induced pancreatic beta-cell dysfunction.The aim of this study was to further dissect the signaling pathway of this process in pancreatic beta-cell line HIT-T15 cells and primary mouse islets.We found that PGE(2) time-dependently increased the c-Jun N-terminal kinase(JNK) pathway activity.JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion(GSIS).PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear localization and transactivation of FOXO1.Activation of FOXO1 induced nuclear exclusion but had no obvious effect on the whole-cell protein level of pancreatic and duodenal homeobox 1(PDX1).However, these effects were all attenuated by JNK inhibition.Furthermore, adenovirus-mediated overexpression of dominant-negative(DN)FOXO1 abolished whereas constitutively active(CA)-FOXO1 mimicked the effects of PGE(2) on GSIS in isolated mouse islets.In addition, we demonstrated that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1 luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN-JNK1 rescued PGE(2)-impaired GSIS in mouse islets.Our results revealed that activation of the JNK is involved in PGE(2)induced beta-cell dysfunction.PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells. 展开更多
关键词 前列腺素 细胞 蛋白质 治疗方法
下载PDF
P-glycoprotein regulating biphasic insulin secretion in rat pancreatic beta cells 被引量:4
14
作者 TANG Yun-zhao LI Dai-qing SUN Fu-jun LI Li YU De-min 《Chinese Medical Journal》 SCIE CAS CSCD 2009年第21期2587-2592,共6页
Background A 65-kD mdrl (multi-drug resistance protein 1, P-glycoprotein)-Iike protein has been suggested to be the regulatory protein to the chloride channel protein 3 (CIC-3) mediating insulin granules acidifica... Background A 65-kD mdrl (multi-drug resistance protein 1, P-glycoprotein)-Iike protein has been suggested to be the regulatory protein to the chloride channel protein 3 (CIC-3) mediating insulin granules acidification and release in mouse pancreatic beta cells. But the protein has not been deeply investigated. In this study, we identified existence of the 65-kda protein in rat islets and preliminarily explored its biological functions. Methods Total RNAs of rat kidneys served as positive controls, and pancreas, islets and INS-1 cells were extracted for reverse-transcript PCR (RT-PCR), respectively. The cDNAs were run with specific primers selected from the mRNA of abcblb encoding P-glycoprotein. All PCR products were visualized in agarose gel electrophoresis and sequenced. Homogenates of rat islets and INS-1 cells were applied to SDS-PAGE. P-glycoprotein was detected by a specific monoclonal antibody, C219. Biphasic insulin release was measured in static incubations of rat islets with radioimmunology assay. Results Compared with positive control, expression of the P-glycoprotein mRNA segments were detected in the islets, INS-1 cells and pancreas. Sequence analysis confirmed that the PCR products were matched with mRNA of P-glycoprotein. A 65-kda protein was recognized by the antibody in the islets homogenate but not in that of INS-1 cells in Western-blotting. Instead, the homogenate of INS-1 cells contained a 160-kda protein recognized by the antibody. Insulin secretion of rat islets were stimulated by high glucose (16.7mmol/L), and showed biphasic curve during 60-minute incubation. After co-incubation with cyclosporine A (CsA), specific inhibitor to P-glycoprotein, the second phase of insulin secretion was reduced significantly while the first phase was not influenced. Conclusions The 65-kda protein expressed in rat islets is most likely a mini-P-glycoprotein. It may play a key role regulating biphasic insulin release. 展开更多
关键词 pancreatic beta cell ISLET P-GLYCOPROTEIN biphasic insulin secretion
原文传递
重构腺相关病毒转导PDX-1对C2C12分化为胰岛素分泌细胞的作用 被引量:3
15
作者 杨川 李莉 +4 位作者 王川 陈黎红 黎峰 严励 程桦 《中山大学学报(医学科学版)》 CAS CSCD 北大核心 2006年第5期486-490,共5页
【目的】重构含有PDX-1的腺相关病毒载体,将PDX-1转导入C2C12细胞,观察胰岛素分泌量的改变。【方法】应用PCR方法将PDX-1从pZL1质粒中克隆出来,安装到Stratagene公司的腺相关病毒(AAVHelper-FreeSystem)表达系统中,转染HEK293细胞,培养7... 【目的】重构含有PDX-1的腺相关病毒载体,将PDX-1转导入C2C12细胞,观察胰岛素分泌量的改变。【方法】应用PCR方法将PDX-1从pZL1质粒中克隆出来,安装到Stratagene公司的腺相关病毒(AAVHelper-FreeSystem)表达系统中,转染HEK293细胞,培养72h,提取病毒悬液,转导PDX-1进入C2C12细胞中,检测细胞培养液中的胰岛素含量。【结果】①用X-gal染色系统检测,可见有蓝色的阳性细胞。②病毒的粗略的浓度经计算后大约为1012/mL,转导的病毒数约为1011。③PCR结果:用重构的腺相关病毒转导后C2C12有胰岛素及PDX-1的mRNA的表达。④用重构的腺相关病毒转导PDX-1进入C2C12后的培养液的胰岛素浓度为(5.5±1.1)μIU/mL,较其他方法也有较明显的增加(P<0.05)。【结论】通过应用含有PDX-1基因的重构腺相关病毒载体可以转导PDX-1在C2C12细胞中表达,且可以提高C2C12分化为胰岛素分泌细胞的分泌量。 展开更多
关键词 PDX-1 成肌细胞 胰岛素分泌细胞 腺相关病毒
下载PDF
枸杞多糖通过抑制H_2O_2诱导的INS-1细胞凋亡促进胰岛素分泌 被引量:5
16
作者 张学军 尹长江 +2 位作者 杨坤宝 张海峰 史华宁 《中国中医基础医学杂志》 CAS CSCD 北大核心 2014年第9期1215-1217,共3页
目的:探讨枸杞多糖对H2O2诱导胰岛INS-1细胞凋亡和胰岛素分泌功能的影响。方法:采用H2O2诱导INS-1细胞凋亡模型,用100 mg/L枸杞多糖处理INS-1细胞,MTT法检测细胞活力,放射免疫法检测胰岛素含量,流式细胞仪检测细胞凋亡,荧光定量PCR检测B... 目的:探讨枸杞多糖对H2O2诱导胰岛INS-1细胞凋亡和胰岛素分泌功能的影响。方法:采用H2O2诱导INS-1细胞凋亡模型,用100 mg/L枸杞多糖处理INS-1细胞,MTT法检测细胞活力,放射免疫法检测胰岛素含量,流式细胞仪检测细胞凋亡,荧光定量PCR检测Bcl-2、Bax和Caspase-3的mRNA表达。结果 100 mg/L枸杞多糖能明显提高H2O2处理INS-1细胞的活力(P<0.01),促进细胞基础和葡萄糖刺激的胰岛素分泌(P<0.05,P<0.01),减少细胞凋亡(P<0.01),同时Bcl-2的表达明显升高(P<0.01),Bax和Caspase-3的表达明显降低(P<0.01,P<0.01)。结论:枸杞多糖可能通过促进Bcl-2的表达,抑制Bax和Caspase-3的表达,以降低H2O2诱导的INS-1凋亡,同时促进INS-1细胞的胰岛素分泌。 展开更多
关键词 枸杞多糖 INS-1 细胞凋亡 胰岛素分泌
下载PDF
PDX-1对成肌细胞株C2C12分化为胰岛素分泌细胞的作用 被引量:4
17
作者 杨川 程桦 +3 位作者 王川 严励 黎锋 魏菁 《中山大学学报(医学科学版)》 CAS CSCD 北大核心 2005年第4期409-412,共4页
【目的】探讨PDX-1对成肌细胞株C2C12分化为胰岛素分泌细胞的作用。【方法】将C2C12细胞分别经过不同浓度的类胰高血糖素(GLP-1)诱导120h后,瞬间转染胰腺十二指肠同源框(PDX-1)基因,用RT-PCR检测PDX-1的表达,流式细胞仪、放射免疫法检... 【目的】探讨PDX-1对成肌细胞株C2C12分化为胰岛素分泌细胞的作用。【方法】将C2C12细胞分别经过不同浓度的类胰高血糖素(GLP-1)诱导120h后,瞬间转染胰腺十二指肠同源框(PDX-1)基因,用RT-PCR检测PDX-1的表达,流式细胞仪、放射免疫法检测细胞内和培养基中是否存在胰岛素。【结果】GLP-1可以直接诱导C2C12细胞表达PDX-1;PDX-1瞬时转染C2C12细胞后,胰岛素分泌细胞阳性率比值(1.19±0.10)、培养基中的胰岛素含量(2.45±1.48)×10-6U/mL均明显升高(P<0.05);单独的40nmol/LGLP-1诱导与瞬间转染PDX-1相比,阳性率比值及胰岛素浓度的差别均无统计学意义。【结论】GLP-1可以诱导C2C12表达PDX-1,而且PDX-1可以促进C2C12分泌胰岛素。提示GLP-1诱导C2C12分化为胰岛素分泌细胞可能与PDX-1有关。 展开更多
关键词 胰岛素分泌细胞 PDX-1 成肌细胞株 分化 C2C12细胞 GLP-1 RT-PCR检测 胰腺十二指肠 胰高血糖素 流式细胞仪 免疫法检测 胰岛素含量 mol/L 胰岛素浓度 分泌胰岛素 不同浓度 细胞表达 瞬时转染 培养基 阳性率 同源框 细胞内
下载PDF
中药单体成分大黄素对胰岛β细胞NIT-1的影响 被引量:3
18
作者 马晓莉 汪保安 +1 位作者 邹效漫 母义明 《中国现代医学杂志》 CAS CSCD 北大核心 2008年第7期873-875,共3页
目的研究中药提取的单体成分大黄素对胰岛β细胞NIT-1增殖、凋亡及胰岛素分泌作用的影响。方法不同浓度的大黄素分别作用于NIT-1细胞不同时间。以MTT法检测细胞的增殖活性;收集细胞,以Annexin V/PI染色,经流式细胞术检测细胞凋亡发生率... 目的研究中药提取的单体成分大黄素对胰岛β细胞NIT-1增殖、凋亡及胰岛素分泌作用的影响。方法不同浓度的大黄素分别作用于NIT-1细胞不同时间。以MTT法检测细胞的增殖活性;收集细胞,以Annexin V/PI染色,经流式细胞术检测细胞凋亡发生率;收集细胞培养上清液测定基础和高糖刺激后胰岛素分泌量。结果2.5μg/mL大黄素作用于NIT-1细胞时对其增殖无明显影响,5.0μg/mL以上对NIT-1细胞增殖的影响呈时间和剂量依赖性降低(P<0.01);0~25.0μg/mL大黄素分别作用于NIT-1细胞24h后,细胞凋亡率呈浓度依赖性增加(P<0.05);0~5.0μg/mL大黄素分别作用于NIT-1细胞24h后,基础胰岛素分泌量呈浓度依赖性降低(P<0.05);高糖刺激后胰岛素分泌量在大黄素0和2.5μg/mL组间无差别,而在5.0μg/mL组则明显降低(P<0.05)。结论大黄素可诱导胰岛细胞凋亡,并抑制胰岛素分泌。 展开更多
关键词 大黄素 胰岛细胞凋亡 胰岛素分泌
下载PDF
高浓度葡萄糖对体外培养小鼠胰岛细胞NF-κB的表达及细胞凋亡的影响 被引量:3
19
作者 梁瑜祯 张木勋 +2 位作者 夏宁 杨月莲 冯乐平 《吉林大学学报(医学版)》 CAS CSCD 北大核心 2009年第2期233-237,398,F0003,共7页
目的:探讨核因子κB(NF-κB)在高浓度葡萄糖诱导胰岛细胞凋亡中的作用。方法:对分离纯化的小鼠胰腺胰岛细胞进行体外培养,按DMEM培养液里葡萄糖浓度不同,分为6组:G1组(5.6mmol·L-1葡萄糖)、G2组(7.8mmol·L-1)、G3组(11.1mmol&... 目的:探讨核因子κB(NF-κB)在高浓度葡萄糖诱导胰岛细胞凋亡中的作用。方法:对分离纯化的小鼠胰腺胰岛细胞进行体外培养,按DMEM培养液里葡萄糖浓度不同,分为6组:G1组(5.6mmol·L-1葡萄糖)、G2组(7.8mmol·L-1)、G3组(11.1mmol·L-1)、G4组(16.7mmol·L-1)、G5组(22.2mmol·L-1)及G6组(27.6mmol·L-1)。采用放射免疫法检测各组胰岛细胞胰岛素分泌水平;免疫组织化学染色法检测NF-κB活性;免疫荧光法检测细胞色素C释放和细胞核染色检测细胞凋亡。结果:当葡萄糖浓度5.6~11.1mmol·L-1时,随着葡萄糖浓度升高,胰岛细胞胰岛素分泌逐渐增加(P<0.05),NF-κB的活性逐渐增加(P<0.05),但此时细胞凋亡未见显著的变化(P>0.05),细胞色素C释放的组间比较差异无显著性(P>0.05)。当葡萄糖浓度≥16.7mmol·L-1时,与葡萄糖浓度≤11.1mmol·L-1各组比较,NF-κB表达明显增加,细胞色素C的释放也逐渐增强(P<0.05),胰岛细胞凋亡百分率同时也呈明显增加趋势(P<0.05)。结论:高浓度葡萄糖可以诱导胰岛细胞NF-κB表达增加,细胞色素C释放增强,同时诱导胰岛细胞凋亡,提示NF-κB的激活与胰岛细胞凋亡可能存在必然的联系,抑制NF-κB活性可能对于保护胰岛细胞有重要作用。 展开更多
关键词 胰岛分泌细胞 细胞凋亡 高浓度葡萄糖 NF-ΚB 细胞色素C类
下载PDF
高浓度葡萄糖对PDX-1表达和胰岛素分泌功能的影响 被引量:4
20
作者 肖常青 邓宏明 黄媛 《中国糖尿病杂志》 CAS CSCD 北大核心 2006年第4期281-283,共3页
目的探讨高浓度葡萄糖(Glu)对PDX-1表达的影响及其与胰岛素(Ins)分泌的关系。方法分别测定SD大鼠胰岛细胞基础和Glu刺激后Ins分泌量、细胞内Ins含量、细胞内PDX-1mRNA和蛋白的表达水平。结果1·高糖刺激3天后,基础和Glu刺激后Ins分... 目的探讨高浓度葡萄糖(Glu)对PDX-1表达的影响及其与胰岛素(Ins)分泌的关系。方法分别测定SD大鼠胰岛细胞基础和Glu刺激后Ins分泌量、细胞内Ins含量、细胞内PDX-1mRNA和蛋白的表达水平。结果1·高糖刺激3天后,基础和Glu刺激后Ins分泌量、细胞内Ins含量及PDX-1蛋白表达水平均明显降低(P<0·01)。2·在高糖环境下,延长培养时间可显著加强高糖对PDX-1蛋白表达的抑制作用。3·纠正高糖环境3天后可部分逆转高糖对PDX-1蛋白表达的抑制作用。结论高浓度Glu对PDX-1蛋白表达的抑制是Glu毒性作用的机制之一,纠正高糖3天后可部分逆转高糖对PDX-1蛋白表达的抑制作用,恢复Ins分泌功能。 展开更多
关键词 PDX-1 胰岛素分泌 胰岛细胞培养
下载PDF
上一页 1 2 16 下一页 到第
使用帮助 返回顶部