Type II diabetes mellitus (Bos taurus)

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FFAObesityAdipoctokine signaling pathwayType II diabetes mellitus+py (tyrosine phosphorylation)Impaired Insulin SecretionCa 2+ dependentPancreatic beta cellPrevention of membrane depolarizationInsulin signaling pathwayGlucose ( hyperglycemia)Maturity onsetdiabetes of the youngK+obesitytransient hyperglycemia hyperinsulinismglycation, hexosamine pathway,respiratory chain+ps (serine phosphorylation)Insulin ResistanceAdipotocyte, heptocyte, skeletal muscle cell Adipocytokine Signaling PathwayDNAROSSLC2A4SOCS4MAPK1GKPHKA2PRKCZPRKCDSURF1MAFAPDX1MAPK8INSKCNJ11ATPCa2+MAPK8MTORIKBKBPyruvateIR-AADIPOQApoptosisIRS1CACNA1APIK3R5INSTNFGlucoseIRS1SLC2A2


Description

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.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP1584(72094) with a 100.0% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

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History

CompareRevisionActionTimeUserComment
105918view11:45, 16 August 2019MaintBotHMDB identifier normalization
80662view15:21, 30 June 2015MkutmonNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADIPOQGeneProductENSBTAG00000019813 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000181092
ATPMetaboliteHMDB0000538 (HMDB)
ApoptosisPathwayWP254 (WikiPathways)
CACNA1AGeneProductENSBTAG00000014828 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000141837
Ca2+MetaboliteHMDB0000464 (HMDB)
GKGeneProductENSBTAG00000008124 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000198814
GlucoseMetaboliteHMDB0000122 (HMDB)
IKBKBGeneProductENSBTAG00000007599 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000104365
INSGeneProductENSBTAG00000013003 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000129965
IR-AGeneProductENSBTAG00000012687 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000171105
IRS1GeneProductENSBTAG00000021308 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000169047
KCNJ11GeneProductENSBTAG00000016170 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000187486
MAFAGeneProductENSBTAG00000026344 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000182759
MAPK1GeneProductENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000100030
MAPK8GeneProductENSBTAG00000007876 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000107643
MTORGeneProductENSBTAG00000015325 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000198793
PDX1GeneProductENSBTAG00000010690 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000139515
PHKA2GeneProductENSBTAG00000015355 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000044446
PIK3R5GeneProductENSBTAG00000005978 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000141506
PRKCDGeneProductENSBTAG00000008719 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000163932
PRKCZGeneProductENSBTAG00000014119 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000067606
PyruvateMetaboliteHMDB0000243 (HMDB)
SLC2A2GeneProductENSBTAG00000005386 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000163581
SLC2A4GeneProductENSBTAG00000009190 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000181856
SOCS4GeneProductENSBTAG00000021988 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000180008
SURF1GeneProductENSBTAG00000030384 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000148290
TNFGeneProductENSBTAG00000025471 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000232810

Annotated Interactions

No annotated interactions
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