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].f81e75f9ef43diabetes mellitusDOID:9351Disease11078440PubMedTriggering and amplifying pathways of regulation of insulin secretion by glucose.Diabetes2000Henquin JC15733744PubMedPositive and negative regulation of insulin signaling through IRS-1 phosphorylation.Biochimie2005Gual PLe Marchand-Brustel YTanti JFhyperglycemiaDOID:4195Diseasepancreatic beta cellCL:0000169Cell Typedisease pathwayPW:0000013Pathway OntologyhepatocyteCL:0000182Cell Typetype 2 diabetes mellitus pathwayPW:0000208Pathway OntologyadipocyteCL:0000136Cell Type11272200PubMedRole of apoptosis in pancreatic beta-cell death in diabetes.Diabetes2001Chandra JZhivotovsky BZaitsev SJuntti-Berggren LBerggren POOrrenius S15759102PubMedOxidative stress, ER stress, and the JNK pathway in type 2 diabetes.J Mol Med (Berl)2005Kaneto HMatsuoka TANakatani YKawamori DMiyatsuka TMatsuhisa MYamasaki Ycell of skeletal muscleCL:0000188Cell Type