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

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

ELIAS MEEZAN的其他文献

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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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