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Study on the differentiation and proliferation of GLP-1-producing L cells and the development of new incretin-based therapy for diabetes mellitus

产GLP-1 L细胞分化增殖研究及肠促胰岛素治疗糖尿病新疗法的开发

基本信息

批准号：
20591075
负责人：
MIYAGAWA Jun-Ichiro
金额：
$ 3.08万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

Incretin hormone GLP-1(glucagon-like peptide-1) secreted from gastrointestinal tract has multi-potent physiological actions including increase or maintenance of beta cell mass (promotion of proliferation and neogenesis, and inhibition of apoptosis in beta cells). In addition to the incretin action, these effects that have not been demonstrated in human, are also important in view of regenerative medicine in diabetes mellitus.We studied on the development and differentiation of GLP-1 secreting L cells in mice, and the change in the number of L cells in model mice of type 2 diabetes mellitus. In the intestinal tract, GLP-1-positive cells are difficult to detect in fetal period, and most of them appear in post-natal period, suggesting complicated mechanism for differentiation of L cells requiring endogenous and exogenous factors. Both in vivo and in vitro (GLP-1 secreting L cell line NCI-H716) studies, it was difficult and failed in detecting GLP-1-secretory factors (GLPSF) and L-cell proliferation factors (LCPF) suitable for the development of anti-diabetic drugs. In diabetic mice (db/db mice), relative L cell number appeared to be increased compared to that of control mice which showed the trend to decrease with aging.In human study on the secretory response of incretin hormones (GIP and GLP-1) to oral glucose intake (75g OGTT) in Japanese subjects with normal glucose tolerance, both incretin hormones showed different actions to the change of plasma concentrations of glucose and insulin. The secretory response of GIP correlated positively to insulin secretion, while that of GLP-1 did not, and appeared to be involved at least in part in inhibition glucagon secretion.

由胃肠道分泌的肠促胰岛素激素GLP-1（胰高血糖素样肽-1）具有多功能的生理作用，包括增加或维持β细胞质量（促进β细胞的增殖和新生，以及抑制β细胞的凋亡）。除了肠促胰岛素的作用外，这些在人体中尚未被证实的作用，从糖尿病的再生医学的观点来看也是重要的。我们研究了小鼠中分泌GLP-1的L细胞的发育和分化，以及2型糖尿病模型小鼠中L细胞数量的变化。在肠道中，GLP-1阳性细胞在胎儿期很难检测到，并且大多数在出生后出现，这表明L细胞的分化需要内源性和外源性因素的复杂机制。无论是在体内还是在体外（分泌GLP-1的L细胞系NCI-H716）研究中，都难以检测适合于开发抗糖尿病药物的GLP-1分泌因子（GLPSF）和L细胞增殖因子（LCPF）。糖尿病小鼠（db/db小鼠），相对L细胞数似乎比对照小鼠增加，而对照小鼠随着年龄的增长呈下降趋势。在人类肠促胰岛素激素分泌反应的研究中（GIP和GLP-1）与口服葡萄糖摄入量（75 g OGTT），两种肠促胰岛素激素对血糖和胰岛素浓度变化的作用不同。GIP的分泌反应与胰岛素分泌呈正相关，而GLP-1的分泌反应与胰岛素分泌无关，并且似乎至少部分地参与抑制胰高血糖素分泌。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effect of gliclazide on platelet aggregation and the plasminogen activator inhibitor typel level in type 2 diabetic patients.

格列齐特对2型糖尿病患者血小板聚集和纤溶酶原激活剂抑制剂1型水平的影响。

DOI：
发表时间：
期刊：
Metabolism (In press)
影响因子：
0
作者：
Konya H.;Hasegawa Y.;Hamaguchi T.;Satani K.;Umehara A.;Katsuno T.;Ishikawa T.;Miuchi M.;Kohri K.;Suehiro A.;Kakishita E.;Miyaeawa J.;Namba M.
通讯作者：
Namba M.

(シンポジウム)糖尿病治療での規律と寛容

(研讨会)糖尿病治疗的纪律与耐受