Characterization of Munc13-1 and insulin secretion during pancreatic development in rats

Characterization of Munc13-1 and insulin secretion during pancreatic development in rats
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大鼠胰腺发育过程中 Munc13-1 和胰岛素分泌的特征

DOI:
10.1007/bf03345615
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发表时间:
2008-07
影响因子:
5.4
通讯作者:
Yuan, Q. X.
Yuan, Q. X.
中科院分区:
医学3区
文献类型:
--
作者:
Liu, C.;Guo, J.;Zhou, J. Y.;De, W.;Liu, C. P.;Teng, L. P.;Liu, L. J.;Yuan, Q. X.

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Munc13-1可能是调节胰岛素胞吐的关键因子,但其确切的表达和作用尚不清楚,特别是在胰腺发育过程中。我们试图研究Munc13-1在大鼠胚胎胰腺发育过程中的表达和功能,并确定其对胰岛素分泌的影响。本研究在显微镜下解剖了胚胎12.5天(E12.5)、E15.5、E18.5、新生大鼠、出生后21天(P21)和成年期的大鼠胰腺。对妊娠15天至足月的孕鼠限食50%卡路里建立宫内发育迟缓(IUGR)模型。采用逆转录聚合酶链式反应、实时荧光定量聚合酶链式反应、Western印迹和酶联免疫吸附试验检测Munc13-1的表达和胰岛素分泌。用免疫组织化学和免疫荧光方法确定Munc13-1的定位。我们发现Munc13-1与胰岛素一起位于胰岛。胰岛素和Munc13-1特异性mRNA分别在E12.5和E15.5才检测到,并随着胎儿的发育而增加。Western印迹结果显示,Munc13-1在E15.5和E18.5有低表达,以后有所升高。IUGR新生大鼠的血胰岛素水平和Munc13-1水平较正常大鼠同时降低。这些结果表明,Munc13-1在胎儿发育过程中存在于胰岛中,其在胰腺中的缺失与IUGR时的血胰岛素水平降低相一致。Munc13-1可能在胰岛素胞吐中起重要作用。
Munc13-1 may be a key factor in regulating insulin exocytosis, but its exact expression and role have not been clarified yet, especially during pancreatic development. We attempted to investigate the expression and function of Munc13-1 during embryonic pancreatic development in rats and determine the effects on insulin secretion. In the present study, pancreata of rats at embryonic day 12.5 (E12.5), E15.5, E18.5, new-born, 21 after birth (P21), and adult stage were dissected under microscope. The rat model of intrauterine growth retardation (IUGR) was made by 50% calorie restriction in pregnant rats from gestational day 15 until term. The expression of Munc13-1 and insulin secretion was studied by the techniques of RT-PCR, real-time PCR, Western blot, and enzyme-linked immunosorbent assay. Immunohistochemistry and immunofluorescence were used to define the location of Munc13-1. We found that Munc13-1 was located at islet along with insulin. Insulin- and Munc13-1-specific mRNA were not detected until E12.5 and E15.5, respectively, and increased with the development of the fetus. Western blot showed that Munc13-1 was low at E15.5 and E18.5 and increased later. The blood insulin level and Munc13-1 were reduced simultaneously in IUGR newborn rats compared with normal ones. These results suggest that Munc13-1 exists in pancreas islets during fetus development and its deficiency in the pancreas, as occurs in IUGR, was in accordance with decreased blood insulin level. Munc13-1 may play an essential role in insulin exocytosis.
DOI: 10.1073/pnas.122623799
发表时间: 2002-06-25
影响因子: 11.1
作者:
Varoqueaux, F;Sigler, A;Rosenmund, C
通讯作者: Rosenmund, C
DOI: --
发表时间: 2006
期刊: --
影响因子: --
作者:
Qingxin;Yuan;Chao;Liu;Yah;Zhong;Cuiping;Li;Jinyong;Zhou;Li-ping;Teng;Jingjing;Hu;Wei
通讯作者: Qingxin;Yuan;Chao;Liu;Yah;Zhong;Cuiping;Li;Jinyong;Zhou;Li-ping;Teng;Jingjing;Hu;Wei
DOI: 10.2337/db05-1263
发表时间: 2006-05-01
期刊: DIABETES
影响因子: 7.7
作者:
Kwan, EP;Xie, L;Gaisano, HY
通讯作者: Gaisano, HY
DOI: 10.1074/jbc.m303203200
发表时间: 2003-07
影响因子: 4.8
作者:
L. Sheu;E. Pasyk;J. Ji;Xiaohang Huang;Xiaodong Gao;F. Varoqueaux;N. Brose;H. Gaisano
通讯作者: L. Sheu;E. Pasyk;J. Ji;Xiaohang Huang;Xiaodong Gao;F. Varoqueaux;N. Brose;H. Gaisano
DOI: 10.1128/mcb.25.14.5973-5984.2005
发表时间: 2005-07-01
影响因子: 5.3
作者:
Varoqueaux, F;Sons, MS;Brose, N
通讯作者: Brose, N