ALLOXAN RESISTANCE & ISLET REGENERATION IN GUINEA PIG
四氧嘧啶耐药性
基本信息
- 批准号:3462880
- 负责人:
- 金额:$ 2.48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1989
- 资助国家:美国
- 起止时间:1989-05-01 至 1994-07-31
- 项目状态:已结题
- 来源:
- 关键词:alloxan autoradiography cell cycle drug adverse effect drug related diabetes mellitus drug resistance glucose transport guinea pigs histochemistry /cytochemistry hormone regulation /control mechanism immunocytochemistry insulin laboratory mouse laboratory rat pancreatic islets radiotracer regeneration tissue /cell culture
项目摘要
The guinea pig is unique in its physiologic and pancreatic
morphological responses to high doses of diabetogen alloxan.
Pancreatic B cells of alloxan-treated guinea pigs degenerate, with
large numbers of islet cells demonstrating pyknotic nuclei, loss
of over 50% of immunostainable B cells, and a marked reduction in
serum insulin levels. This is followed, within 72 hrs, by
reappearance of a full complement of immunohistochemically staining
B cells, and, within 14 days, by restoration of normal serum in-
sulin levels. The proposed research will explore the mechanism of
B cell regeneration in the alloxan-treated guinea pig. 3H-
thymidine labeling combined with immunohistochemistry will be
employed to determine: A) whether the regenerated B cells arise
mitotically; B) the nature of the progenitors of B cells; C)
conditions (including age) which modulate the B cell regeneration.
Since we have previously demonstrated that guinea pig B cells do
not regenerate following alloxan treatment in vitro, we will also
attempt to identify serum and pancreatic factors which can
stimulate B-cell regeneration following alloxan-induced B-cell loss
in cultures of guinea pig islet cells. Monoclonal antibodies will
be raised to cell surface antigens of islets isolated from alloxan-
treated regenerating guinea pig pancreas to determine if there is
a unique cell population which serves as the source of the
regenerated cells, and whether such cells are present in normal and
diabetic human pancreas. Alloxan toxicity is due at least in part
to free radical damage to B cells. Since guinea pig B cells are
relatively resistant to low doses of alloxan, we will use in vitro
techniques to determine whether they are resistant to free radical
damage via elevated superoxide dismutase levels. Studies of B-cell
regeneration and replication of B cells are of great importance to
diabetes research. The cultured islet cell system provides both
a useful model for the understanding of B-cell differentiation and
regeneration following injury, and a sensitive in vitro bioassay
for humoral and/or paracrine factors which may stimulate such
processes.
豚鼠在生理和胰腺方面是独特的,
对高剂量糖尿病原四氧嘧啶的形态学反应。
四氧嘧啶处理豚鼠的胰腺B细胞退化,
大量胰岛细胞显示核固缩,丢失
超过50%的免疫缺陷B细胞,
血清胰岛素水平 接下来,在72小时内,
完全化学染色的再现
B细胞,并在14天内,通过恢复正常血清-
胰岛素水平。 拟议的研究将探索
四氧嘧啶处理豚鼠的B细胞再生。 3H-
胸苷标记结合免疫组化,
用于确定:A)再生的B细胞是否出现
有丝分裂; B)B细胞的祖细胞的性质; C)
调节B细胞再生的条件(包括年龄)。
由于我们先前已经证明豚鼠B细胞
在体外四氧嘧啶治疗后不能再生,我们还将
试图确定血清和胰腺因子,
在四氧嘧啶诱导B细胞损失后刺激B细胞再生
在豚鼠胰岛细胞培养物中。 单克隆抗体将
从四氧嘧啶中分离的胰岛的细胞表面抗原,
处理再生豚鼠胰腺,以确定是否有
一种独特的细胞群,
再生细胞,以及这些细胞是否存在于正常和
糖尿病患者的胰腺 四氧嘧啶的毒性至少部分是由于
自由基对B细胞的损害。 因为豚鼠B细胞
相对抵抗低剂量的四氧嘧啶,我们将使用体外
技术,以确定他们是否抵抗自由基
超氧化物歧化酶水平升高造成的损害。 B细胞研究
B细胞的再生和复制对于
糖尿病研究 培养的胰岛细胞系统提供了
一个有用的模型,用于理解B细胞分化和
损伤后的再生以及灵敏的体外生物测定
体液和/或旁分泌因素,可能刺激这种
流程.
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Synthetic guinea pig insulin B-chain C-terminal decapeptide: a novel immunogen for generating immunocytochemical-grade antisera.
合成豚鼠胰岛素 B 链 C 端十肽:一种用于产生免疫细胞化学级抗血清的新型免疫原。
- DOI:10.1177/39.11.1918931
- 发表时间:1991
- 期刊:
- 影响因子:0
- 作者:Maimon,J;Mauro,M;Gorray,KC;Schneider,BS
- 通讯作者:Schneider,BS
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