CELLULAR ACTION OF ALKYLGLYCOSIDES AS GLYCOGEN PRIMERS
烷基糖苷作为糖原引物的细胞作用
基本信息
- 批准号:2906131
- 负责人:
- 金额:$ 16.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-08-05 至 2001-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The regulation of glycogen metabolism is deranged in both Type I and
Type II diabetes mellitus. Glycogen metabolism is impaired in insulin-
sensitive tissues, primarily in skeletal muscle and liver, so that the
synthesis of this glucose storage compound is inadequate to meet the
demands of hyperglycemia. Glycogenin is a self-glycosylating enzyme
which has recently been shown to serve as the core protein for glycogen
synthesis by transferring glucose to itself to form a protein-linked
oligosaccharide chain which serves as a primer for glycogen synthase to
assemble the glycogen molecule. We have recently demonstrated that
several alkylglycosides serve as acceptors for glucose transfer mediated
by enzyme preparations of both glycogenin and glycogen synthase and have
shown that these compounds increase glucose incorporation in liver and
diaphragm of mice. They therefore have the potential to serve as
artificial primers for the synthesis of glycogen. The principal
objective of this proposal is to demonstrate that alkylglucosides and
alkylmaltosides can initiate the synthesis of alpha 1 greater than 4
linked maltooligosaccharide chains in cultured skeletal muscle (L6) and
liver (HEP-G2) cells and thereby modulate the synthesis of glycogen in
these cells.We propose to determine the activities of glycogenin and
glycogen synthesis in cell-free extracts of these cells and demonstrate
that the alkylglycosides will serve as substrates for glucose transfer
by these enzymes. We will then establish that the alkylglycosides will
serve as acceptor substrates for glucose addition in intact cells and
characterize the alkylmaltooligosaccharide products produced as a result
of such addition. The effects of alkylglycosides on glycogenin and
glycogen synthase activities and on glycogen synthesis will also be
determined as will the effects on glucose transport and the influence
of ambient glucose concentrations and insulin on the glucosylation of
alkylglycosides and on glycogen synthesis in these cells. Any effects
of the alkylglycosides on the molecular size and structure of glycogen
synthesized will also be investigated. Significant findings in cultured
cells will be correlated with the effects of the compounds in vivo in
the ob/ob mouse model of NIDDM. The goal of these studies will be to
elucidate how the alkylglycosides serve as exogenous acceptors for
glucose transfer mediated by glycogenin and glycogen synthase in intact
cells and therefore initiate and/or modulate the biosynthesis of
glycogen. These studies may have therapeutic implications for modulating
the disposal of glucose in diabetes.
糖原代谢的调节在I型和
项目成果
期刊论文数量(0)
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ELIAS MEEZAN其他文献
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{{ truncateString('ELIAS MEEZAN', 18)}}的其他基金
CELLULAR ACTION OF ALKYLGLYCOSIDES AS GLYCOGEN PRIMERS
烷基糖苷作为糖原引物的细胞作用
- 批准号:
2693192 - 财政年份:1998
- 资助金额:
$ 16.73万 - 项目类别:
CELLULAR ACTION OF ALKYLGLYCOSIDES AS GLYCOGEN PRIMERS
烷基糖苷作为糖原引物的细胞作用
- 批准号:
6177757 - 财政年份:1998
- 资助金额:
$ 16.73万 - 项目类别:
RENAL PROTEOGLYCANS--EFFECTS OF DIABETES AND HYPERTROPHY
肾蛋白聚糖——糖尿病和肥大的影响
- 批准号:
3239884 - 财政年份:1987
- 资助金额:
$ 16.73万 - 项目类别:
RENAL PROTEOGLYCANS--EFFECTS OF DIABETES AND HYPERTROPHY
肾蛋白聚糖——糖尿病和肥大的影响
- 批准号:
3239883 - 财政年份:1987
- 资助金额:
$ 16.73万 - 项目类别:
RENAL PROTEOGLYCANS--EFFECTS OF DIABETES AND HYPERTROPHY
肾蛋白聚糖——糖尿病和肥大的影响
- 批准号:
3239882 - 财政年份:1987
- 资助金额:
$ 16.73万 - 项目类别:
RENAL PROTEOGLYCANS--EFFECTS OF DIABETES AND HYPERTROPHY
肾蛋白聚糖——糖尿病和肥大的影响
- 批准号:
3239880 - 财政年份:1987
- 资助金额:
$ 16.73万 - 项目类别:
ROLE OF SULFATION IN THE PATHOLOGY OF CYSTIC FIBROSIS
硫酸化在囊性纤维化病理学中的作用
- 批准号:
3233201 - 财政年份:1987
- 资助金额:
$ 16.73万 - 项目类别:
ROLE OF SULFATION IN THE PATHOLOGY OF CYSTIC FIBROSIS
硫酸化在囊性纤维化病理学中的作用
- 批准号:
3233203 - 财政年份:1987
- 资助金额:
$ 16.73万 - 项目类别:
ROLE OF SULFATION IN THE PATHOLOGY OF CYSTIC FIBROSIS
硫酸化在囊性纤维化病理学中的作用
- 批准号:
3233195 - 财政年份:1987
- 资助金额:
$ 16.73万 - 项目类别:
ROLE OF SULFATION IN THE PATHOLOGY OF CYSTIC FIBROSIS
硫酸化在囊性纤维化病理学中的作用
- 批准号:
3233202 - 财政年份:1987
- 资助金额:
$ 16.73万 - 项目类别:
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