Type II diabetes mellitus

Insulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Serine/threonine phosphorylation, interaction with SOCS, regulation of the expression, modification of the cellular localization, and degradation represent the molecular mechanisms stimulated by them. Various kinases (ERK, JNK, IKKbeta, PKCzeta, PKCtheta and mTOR) are involved in this process. The development of type II diabetes requires impaired beta-cell function. Chronic hyperglycemia has been shown to induce multiple defects in beta-cells. Hyperglycemia has been proposed to lead to large amounts of reactive oxygen species (ROS) in beta-cells, with subsequent damage to cellular components including PDX-1. Loss of PDX-1, a critical regulator of insulin promoter activity, has also been proposed as an important mechanism leading to beta-cell dysfunction. Although there is little doubt as to the importance of genetic factors in type II diabetes, genetic analysis is difficult due to complex interaction among multiple susceptibility genes and between genetic and environmental factors. Genetic studies have therefore given very diverse results. Kir6.2 and IRS are two of the candidate genes. It is known that Kir6.2 and IRS play central roles in insulin secretion and insulin signal transmission, respectively. Source: [http://www.kegg.jp/dbget-bin/www_bget?pathway+map04930 KEGG] Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP1584 CPTAC Assay Portal].

胰岛素抵抗与II型糖尿病的关联性极为紧密。所谓‘糖尿病诱发因素’包括游离脂肪酸（FFA）、肿瘤坏死因子α（TNFalpha）及细胞应激等，它们通过抑制胰岛素受体底物1（IRS1）的功能诱导胰岛素抵抗。这些因素激活的分子机制包括丝氨酸/苏氨酸磷酸化、与SOCS的相互作用、表达调控、细胞定位修饰以及降解等。在这一过程中，多种激酶（如ERK、JNK、IKKbeta、PKCzeta、PKCtheta和mTOR）均参与其中。II型糖尿病的发展需要胰岛β细胞功能的损伤。慢性高血糖已被证实可诱导胰岛细胞出现多种缺陷。高血糖被认为可导致β细胞内产生大量的活性氧（ROS），进而损害包括PDX-1在内的细胞成分。PDX-1作为胰岛素启动子活性的关键调节因子，其丢失也被提出是导致胰岛细胞功能障碍的重要机制之一。尽管对遗传因素在II型糖尿病中的重要性没有太多疑问，但由于多个易感基因之间的复杂相互作用以及遗传与环境因素之间的相互作用，遗传分析变得十分困难。因此，遗传学研究的结果差异极大。Kir6.2和IRS是其中的候选基因。已知Kir6.2和IRS在胰岛素分泌和胰岛素信号传导中分别扮演核心角色。来源：[http://www.kegg.jp/dbget-bin/www_bget?pathway+map04930 KEGG]。该途径上的蛋白质有针对的检测方法，可通过[https://assays.cancer.gov/available_assays?wp_id=WP1584 CPTAC检测门户]获得。