可以患上2型糖尿病的哺乳动物具有类似结构的β-叶粉样蛋白寡合体
Brynn E LeMasters1, Caitlyn R Fields1, Justin P Lomont1
1Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706.
概括
哺乳动物岛屿粉样蛋白多 (IAPP) 结构决定了2型糖尿病的风险. IAPP中的特定β表与敏感物种的细胞毒性和疾病发展相关,解释胰岛素缺乏.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 比较生理学比较生理学
背景情况:
- 哺乳动物岛屿粉样多 (IAPP) 序列影响粉样斑块的形成和2型糖尿病 (T2D) 的发展.
- 人类IAPP形成具有特定平行β片结构 (残留物23FGAIL28S) 的有毒寡合体,涉及T2D病原体.
研究的目的:
- 调查不同哺乳动物物种IAPP介导的细胞毒性和T2D倾向的结构基础.
- 为了确定G24残留的β片形成是否与哺乳动物T2D发育相关.
主要方法:
- 利用二维红外光谱来监测七种哺乳动物中的IAPP结构.
- 在G24采用同位素标记,以检测特定的寡合体β叶形成.
- 在有或没有T2D倾向的物种中评估IAPP细胞毒性.
主要成果:
- 发展T2D的物种在纤维细胞形成前的滞后阶段表现出具有G24β表的细胞毒性IAPP.
- 抵抗T2D的物种显示无毒的IAPP缺乏特征性的G24β-sheet.
- 猪IAPP形成了不同的,无毒的寡合体,与T2D相关的人类IAPP结构不同.
结论:
- 在IAPP寡合体中G24处存在平行β片的存在与哺乳动物中细胞毒性和T2D易感性相关.
- 在IAPP的20-29区域的氨基酸序列决定了寡合体结构,毒性和T2D倾向.
- 这种结构相关性为T2D晚期胰岛素缺乏症提供了另一种解释,超出了粉样斑块的形成.
更多相关视频
10:19Neurodegeneration in an Animal Model of Chronic Amyloid-beta Oligomer Infusion Is Counteracted by Antibody Treatment Infused with Osmotic Pumps
Published on: August 14, 2016
9.7K
03:17Author Spotlight: Advancing Diabetes Research with Static Exercise Training in Mice
Published on: March 29, 2024
1.0K
相关概念视频
Diabetes Mellitus: Type 2 and Gestational
4.7K
Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
4.7K
Amyloid Fibrils
11.9K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
11.9K
Diabetes Mellitus: Overview and Type I Subtype
5.2K
Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
5.2K
Protein and Protein Structure
87.4K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
87.4K
Fruit Development, Structure, and Function
25.1K
Fruits form from a mature flower ovary. As seeds develop from the ovules contained within, the ovary wall undergoes a series of complex changes to form fruit. In some fruits, such as soybeans, the ovary wall dries; in other fruits, such as grapes, it remains fleshy. In some cases, organs other than the ovary contribute to fruit formation; such fruits are called accessory fruits.
25.1K
Seed Structure and Early Development of the Sporophyte
31.0K
Seed structures are composed of a protective seed coat surrounding a plant embryo, and a food store for the developing embryo. The embryo contains the precursor tissues for leaves, stem, and roots. The endosperm and cotyledons—seed leaves—act as the food reserves for the growing embryo.
31.0K
