Type II diabetes mellitus (WP3117)

Bos taurus

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.

Authors

Martina Summer-Kutmon

Activity

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Organisms

Bos taurus

Communities

Annotations

Disease Ontology

hyperglycemia type 2 diabetes mellitus

Pathway Ontology

type 2 diabetes mellitus pathway

Cell Type Ontology

type B pancreatic cell

Participants

Label Type Compact URI Comment
Ca2+ Metabolite hmdb:HMDB0000464
Pyruvate Metabolite hmdb:HMDB0000243
ATP Metabolite hmdb:HMDB0000538
Glucose Metabolite hmdb:HMDB0000122
KCNJ11 GeneProduct ensembl:ENSBTAG00000016170 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000187486
TNF GeneProduct ensembl:ENSBTAG00000025471 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000232810
IR-A GeneProduct ensembl:ENSBTAG00000012687 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000171105
MAPK1 GeneProduct ensembl:ENSBTAG00000010312 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000100030
MAFA GeneProduct ensembl:ENSBTAG00000026344 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000182759
SLC2A4 GeneProduct ensembl:ENSBTAG00000009190 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000181856
SLC2A2 GeneProduct ensembl:ENSBTAG00000005386 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000163581
PRKCZ GeneProduct ensembl:ENSBTAG00000014119 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000067606
INS GeneProduct ensembl:ENSBTAG00000013003 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000129965
PIK3R5 GeneProduct ensembl:ENSBTAG00000005978 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000141506
ADIPOQ GeneProduct ensembl:ENSBTAG00000019813 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000181092
PHKA2 GeneProduct ensembl:ENSBTAG00000015355 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000044446
MAPK8 GeneProduct ensembl:ENSBTAG00000007876 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000107643
GK GeneProduct ensembl:ENSBTAG00000008124 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000198814
IKBKB GeneProduct ensembl:ENSBTAG00000007599 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000104365
CACNA1A GeneProduct ensembl:ENSBTAG00000014828 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000141837
SOCS4 GeneProduct ensembl:ENSBTAG00000021988 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000180008
IRS1 GeneProduct ensembl:ENSBTAG00000021308 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000169047
MTOR GeneProduct ensembl:ENSBTAG00000015325 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000198793
PDX1 GeneProduct ensembl:ENSBTAG00000010690 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000139515
PRKCD GeneProduct ensembl:ENSBTAG00000008719 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000163932
SURF1 GeneProduct ensembl:ENSBTAG00000030384 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000148290

References