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METABOLIC FUELS, DIABETES AND SOMATOMEDIN ACTIVITY

代谢燃料、糖尿病和生长调节素活性

基本信息

批准号：
3152819
负责人：
LAWRENCE S PHILLIPS
金额：
$ 16.29万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-08-01 至 1986-03-31
项目状态：
已结题

项目摘要

Although poor growth in diabetes and malnutrition is attributed to decreased utilization of nutrients, the mechanism of the defect is not known. Skeletal growth is attributed to stimulation of cartilage by somatomedins, circulating factors with broad anabolic effects. Other circulating factors, inhibitors, may limit the actions of somatomedins; bioassay measurements of net somatomedin activity reflect both somatomedins and inhibitors. Our studies suggest that somatomedins and inhibitors can be separated by chromatographic procedures, and that both factors are generated by the liver according to insulin and nutritional status. While alterations in somatomedins and inhibitors might direct utilization of nutrients toward or away from growth, control processes are poorly understood. To elucidate underlying mechanisms, the following efforts are proposed. 1) To assess regulation by insulin and nutrition in vivo, circulating somatomedins and inhibitors will be examined in humans with a) varying diabetic control, b) malnutrition and realimentation, and c) diet-induced weight loss, and d) rats with a wide range of metabolic alterations. 2) To study the liver as the putative locus of regulation, net "formation" of somatomedins and inhibitors will be measured via combined liver extraction and perfusion, and related to probes of hepatic fuel metabolism as the liver responds to a) external homeostatic demands (imposed alterations in insulin and nutrition) and b) internal demands (restoration after partial hepatectomy). 3) To investigate potential modulation of nutrient utilization according to the balance of generated somatomedins and inhibitors, interactions will be examined on cartilage, muscle, and adipose tissue in vitro and in vivo. 4) These physiologic experiments will be accompanied by physicochemical efforts to a) enhance separation and recovery of somatomedins and inhibitors from biological samples, and b) further improve preparations for biological characterization. These studies should provide improved understanding of the regulation of normal growth, insight into the pathophysiology of impaired growth, and new concepts for therapy of growth failure in diabetes mellitus and malnutrition.

虽然生长不良归因于糖尿病和营养不良的减少

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Separation of somatomedins and somatomedin inhibitors by size exclusion high-performance liquid chromatography.

通过尺寸排阻高效液相色谱分离生长调节素和生长调节素抑制剂。

DOI：
10.1016/s0378-4347(00)84668-x
发表时间：
1985
期刊：
Journal of chromatography
影响因子：
0
作者：
Goldstein,S;Stivaletta,LA;Phillips,LS
通讯作者：
Phillips,LS

Pharmacokinetics and monitoring of cyclosporine following orthotopic liver transplantation.

原位肝移植后环孢素的药代动力学和监测。

DOI：
10.1055/s-2008-1040633
发表时间：
1985
期刊：
Seminars in liver disease
影响因子：
4.2
作者：
Venkataramanan,R;Burckhart,GJ;Ptachcinski,RJ
通讯作者：
Ptachcinski,RJ

Antipyrine kinetics in liver disease and liver transplantation.

肝病和肝移植中的安替比林动力学。

DOI：
10.1038/clpt.1986.57
发表时间：
1986
期刊：
Clinical pharmacology and therapeutics
影响因子：
6.7
作者：
Mehta,MU;Venkataramanan,R;Burckart,GJ;Ptachcinski,RJ;Yang,SL;Gray,JA;VanThiel,DH;Starzl,TE
通讯作者：
Starzl,TE

Cyclosporine kinetics in healthy volunteers.

健康志愿者中的环孢菌素动力学。

DOI：
10.1002/j.1552-4604.1987.tb02193.x
发表时间：
1987
期刊：
Journal of clinical pharmacology
影响因子：
2.9
作者：
Ptachcinski,RJ;Venkataramanan,R;Burckart,GJ;Gray,JA;VanThiel,DH;Sanghvi,A;Rosenthal,JT
通讯作者：
Rosenthal,JT

Nutrition, somatomedins, and the brain.

营养、生长激素和大脑。