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Elucidation of the molecular mechanisms underlying insulin and exercise-induced effects on metabolism and vascular cells

阐明胰岛素和运动对代谢和血管细胞影响的分子机制

基本信息

批准号：
16390262
负责人：
ASANO Tomoichiro
金额：
$ 9.22万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390262/
关键词：
insulin Akt Diabetes mellitus insulin resistance resistin AMPK 運動糖輸送担体

项目摘要

Resistin was initially identified as a protein, secreted by adipocytes, which inhibits insulin action and adipose differentiation. The three proteins homologous to resistin were identified and given the names resistin-like molecules (RELM) α, β and γ. Resistin and RELMα are abundantly expressed in adipose, but RELMβ and RELMγ are secreted mainly from the gut. Since nutrient composition greatly affects insulin sensitivity, we investigated the regulatory effects of various nutritional factors in food on the expressions of resistin family proteins.First, mice were given diets with different nutritional compositions (high-carbohydrate, high-protein and high-fat) for two weeks. RELMβ mRNA expression in the intestines was markedly suppressed by the high-protein and high-carbohydrate diets, while slightly but not significantly upregulated by the high-fat diet. In the epididymal fat, resistin expression was unchanged, while RELMβ expression was markedly decreased by the high-carbohydrate diet. Taking into consideration that humans have neither RELMα nor RELMγ, our subsequent studies focused on RELMβ expression. We used the human colon cancer cell line LS174T. Treatments with insulin and TNFα as well as stearic acid, a saturated free fatty acid, upregulated RELMβ expression, while D-glucose downregulated RELMβ. These results suggest RELMβ expression to be regulated directly by nutrients such as glucose and saturated free fatty acids including stearic acid, as well as by hormones including insulin and TNFα. These regulations may play an important role in the nutrient-associated induction of insulin resistance.

抵抗素最初被认为是一种由脂肪细胞分泌的蛋白质，可抑制胰岛素作用和脂肪分化。鉴定出与抵抗素同源的三种蛋白质，并将其命名为抵抗素样分子（RELM）α、β和γ。抵抗素和 RELMα 在脂肪中大量表达，但 RELMβ 和 RELMγ 主要从肠道分泌。由于营养成分极大地影响胰岛素敏感性，我们研究了食物中各种营养因素对抵抗素家族蛋白表达的调节作用。首先，给小鼠喂食不同营养成分（高碳水化合物、高蛋白和高脂肪）的饮食两周。高蛋白和高碳水化合物饮食显着抑制肠道中 RELMβ mRNA 的表达，而高脂肪饮食则轻微但不显着上调。在附睾脂肪中，抵抗素表达没有变化，而高碳水化合物饮食则显着降低了 RELMβ 表达。考虑到人类既没有RELMα也没有RELMγ，我们后续的研究主要集中在RELMβ的表达上。我们使用人类结肠癌细胞系 LS174T。胰岛素和 TNFα 以及硬脂酸（一种饱和游离脂肪酸）治疗上调 RELMβ 表达，而 D-葡萄糖下调 RELMβ 表达。这些结果表明 RELMβ 表达直接受到葡萄糖和饱和游离脂肪酸（包括硬脂酸）等营养物质以及胰岛素和 TNFα 等激素的调节。这些调节可能在营养相关的胰岛素抵抗诱导中发挥重要作用。