Fat Cell Size, Muscle Lipid Infiltration and Insulin Re*
脂肪细胞大小、肌肉脂质渗透和胰岛素再*
基本信息
- 批准号:6786590
- 负责人:
- 金额:$ 57.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-09-30 至 2006-07-31
- 项目状态:已结题
- 来源:
- 关键词:adipocytescell differentiationcell proliferationclinical researchcomputed axial tomographydiabetes mellitus geneticsgender differencegene expressionhuman subjectinsulin sensitivity /resistancelipid disorderlipid metabolismliver metabolismmuscle metabolismnoninsulin dependent diabetes mellitusobesitypolymerase chain reactionstriated musclesweight loss
项目摘要
DESCRIPTION (provided by applicant):
There is growing evidence that the development of Type 2 diabetes is
precipitated by alterations in the partitioning of fat between the adipose
tissue vs. muscle, liver and pancreas. Intracellular accumulation of
triglyceride and fatty acid metabolites leads to acquired insulin signaling
defect and insulin resistance. One can, therefore, hypothesize that the
inability of the adipose organ to expand to accommodate excess calories results
in adipose tissue hypertrophy and Type 2 diabetes in predisposed obese subject.
Such a hypothesis is now clearly supported by the following data: 1) Pima
Indians with larger abdominal fat cells are more likely to develop diabetes
than obesity-matched subjects with smaller fat cells; 2) thiazolidinediones
improve insulin sensitivity by inducing adipocyte differentiation; 3) subjects
with acquired total lipodystrophy (like fatless mice) are severely diabetic; 4)
insulin sensitivity is inversely proportional to the triglyceride content of
the muscle.
In this application, we want to test the following hypotheses: 1) muscle lipid
content correlates positively with abdominal subcutaneous adipocyte size in
Type 2 diabetics and obesity-, sex-, and age-matched nondiabetics; 2) larger
adipocytes are associated with greater weight loss and better improvement in
insulin sensitivity after one year of intensive lifestyle treatment; 3)
expression of genes involved in adipocyte proliferation and differentiation
correlates negatively with adipocyte size in Type 2 diabetic and obesity
matched non-diabetics. In response to weight loss, the expression of these
genes will increase. To test these hypotheses we will perform the following
studies: 1) determine the relationship between abdominal subcutaneous fat cell
size (biopsy) and muscle fat infiltration (CT scan) in 100 subjects from Look
AHEAD Trial and 50 non-diabetic matched for sex, race, age and BMI; 2) identify
the effect of abdominal fat cell size on weight loss and improvement in insulin
sensitivity (hyperglycemic clamp) after one year of intensive lifestyle
treatment in the 100 subjects from the Look AHEAD Trial; 3) quantify in
subcutaneous abdominal adipose tissue the expression of genes involved in
adipocyte proliferation/differentiation in 100 Type 2 diabetic subjects and 50
non-diabetic subjects. Gene expression will also be measured in Type 2
diabetics after one year of intensive lifestyle changes.
描述(由申请人提供):
越来越多的证据表明,2型糖尿病的发展是
通过改变脂肪之间的脂肪分配沉淀
组织对比肌肉肝脏和胰腺的细胞内积累
甘油三酯和脂肪酸代谢产物导致获得性胰岛素信号传导
缺陷和胰岛素抵抗。因此,我们可以假设,
脂肪器官不能扩张以容纳多余的卡路里,
脂肪组织肥大和2型糖尿病。
这样的假设现在得到了以下数据的明确支持:1)皮马
腹部脂肪细胞较大的印度人更容易患糖尿病
与肥胖匹配的受试者相比,脂肪细胞较小; 2)噻唑烷二酮类
通过诱导脂肪细胞分化改善胰岛素敏感性; 3)受试者
获得性总脂肪营养不良(如无脂小鼠)是严重的糖尿病; 4)
胰岛素敏感性与甘油三酯含量成反比,
肌肉。
在本申请中,我们要测试以下假设:1)肌肉脂质
含量与腹部皮下脂肪细胞大小呈正相关,
2型糖尿病患者和肥胖、性别和年龄匹配的非糖尿病患者; 2)较大
脂肪细胞与更大的体重减轻和更好的改善有关,
一年强化生活方式治疗后的胰岛素敏感性; 3)
参与脂肪细胞增殖和分化的基因表达
与2型糖尿病和肥胖的脂肪细胞大小呈负相关
匹配的非糖尿病患者。为了应对减肥,这些表达
基因会增加。为了检验这些假设,我们将执行以下操作
研究:1)确定腹部皮下脂肪细胞之间的关系
100名来自Look的受试者的尺寸(活检)和肌肉脂肪浸润(CT扫描)
AHEAD试验和50名性别、种族、年龄和BMI匹配的非糖尿病患者; 2)确定
腹部脂肪细胞大小对减肥和改善胰岛素的影响
一年强化生活方式后的敏感性(高血糖钳夹)
在Look AHEAD试验的100名受试者中进行治疗; 3)量化
皮下腹部脂肪组织中参与基因表达
100名2型糖尿病受试者和50名2型糖尿病受试者的脂肪细胞增殖/分化
非糖尿病患者。基因表达也将在2型中测量
糖尿病患者经过一年的密集生活方式的改变。
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)
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Eric Ravussin其他文献
Eric Ravussin的其他文献
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{{ truncateString('Eric Ravussin', 18)}}的其他基金
Pennington/Louisiana NORC - Admin Supplement for Pilot and Feasibility studies 2021
彭宁顿/路易斯安那州 NORC - 2021 年试点和可行性研究行政补充
- 批准号:
10399166 - 财政年份:2021
- 资助金额:
$ 57.11万 - 项目类别:
Pennington/Louisiana NORC - Supplement NOT-OD-21-089
彭宁顿/路易斯安那州 NORC - 补充 NOT-OD-21-089
- 批准号:
10408519 - 财政年份:2021
- 资助金额:
$ 57.11万 - 项目类别:
Role of slowly digestible starch in diabetes risk factors in pre-diabetic people
缓慢消化淀粉在糖尿病前期人群糖尿病危险因素中的作用
- 批准号:
8372789 - 财政年份:2012
- 资助金额:
$ 57.11万 - 项目类别:
Role of slowly digestible starch in diabetes risk factors in pre-diabetic people
缓慢消化淀粉在糖尿病前期人群糖尿病危险因素中的作用
- 批准号:
8501442 - 财政年份:2012
- 资助金额:
$ 57.11万 - 项目类别:
Role of Slowly Digestible Starch in Diabetes Risk Factors in Pre-Diabetic People
缓慢消化淀粉在糖尿病前期人群糖尿病危险因素中的作用
- 批准号:
9060311 - 财政年份:2012
- 资助金额:
$ 57.11万 - 项目类别:
Role of slowly digestible starch in diabetes risk factors in pre-diabetic people
缓慢消化淀粉在糖尿病前期人群糖尿病危险因素中的作用
- 批准号:
8668050 - 财政年份:2012
- 资助金额:
$ 57.11万 - 项目类别:
Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women
肥胖女性皮下脂肪分布的细胞动力学
- 批准号:
8666638 - 财政年份:2011
- 资助金额:
$ 57.11万 - 项目类别:
Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women
肥胖女性皮下脂肪分布的细胞动力学
- 批准号:
8440368 - 财政年份:2011
- 资助金额:
$ 57.11万 - 项目类别:
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