Type II diabetes mellitus (Homo sapiens)

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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.

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History

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CompareRevisionActionTimeUserComment
72094view21:35, 24 October 2013Mkutmonupdated datasource for "Apoptosis"
67730view11:55, 26 June 2013DdiglesOntology Term : 'type 2 diabetes mellitus pathway' added !
63481view18:29, 10 May 2013AlexanderPicoFixed Xref for PYK
63274view07:16, 9 May 2013EveloPeriodical save, work in progress
59217view20:13, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
45036view18:50, 6 October 2011KhanspersOntology Term : 'pancreatic beta cell' added !
45034view18:49, 6 October 2011KhanspersOntology Term : 'hyperglycemia' added !
45032view18:47, 6 October 2011KhanspersOntology Term : 'DOID:9351' removed !
45031view18:47, 6 October 2011KhanspersOntology Term : 'type 2 diabetes mellitus' added !
45030view18:47, 6 October 2011KhanspersOntology Term : 'Diabetes' added !
41223view23:45, 1 March 2011MaintBotRemoved redundant pathway information and comments
38693view18:35, 23 September 2010KhanspersChanged layout, connected nodes, added metabolites, added pathway links, fixed arrows
38692view18:26, 23 September 2010KhanspersPeriodical save, work in progress
38690view18:25, 23 September 2010Khanspersperiodical save
38312view22:45, 31 August 2010KhanspersChanged OrganA to Oval
38145view19:00, 17 August 2010KhanspersModified categories
37822view10:08, 6 July 2010AnkuPeriodical save, work in progress
37821view09:55, 6 July 2010AnkuPeriodical save, work in progress
37820view09:44, 6 July 2010AnkuPeriodical save, work in progress
37819view09:34, 6 July 2010AnkuPeriodical save, work in progress
37813view15:05, 5 July 2010AnkuModified description
37812view15:04, 5 July 2010Ankudiabetes type II
37811view14:55, 5 July 2010AnkuPeriodical save, work in progress
37810view14:33, 5 July 2010AnkuPeriodical save, work in progress
37809view14:23, 5 July 2010AnkuPeriodical save, work in progress
37808view14:13, 5 July 2010AnkuPeriodical save, work in progress
37807view14:02, 5 July 2010AnkuPeriodical save, work in progress
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37805view12:17, 5 July 2010AnkuPeriodical save, work in progress
37804view12:06, 5 July 2010AnkuPeriodical save, work in progress
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37802view11:46, 5 July 2010AnkuPeriodical save, work in progress
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37799view11:15, 5 July 2010AnkuPeriodical save, work in progress
37798view11:11, 5 July 2010Ankutype II
37797view11:04, 5 July 2010AnkuPeriodical save, work in progress
37796view10:44, 5 July 2010AnkuNew pathway

External references

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NameTypeDatabase referenceComment
Kir6.2GeneProductENSG00000187486 (Ensembl)
GLUT4GeneProductENSG00000181856 (Ensembl)
PyruvateMetaboliteHMDB00243 (HMDB)
INSRGeneProductENSG00000171105 (Ensembl)
GKGeneProductENSG00000198814 (Ensembl)
INSGeneProductENSG00000129965 (Ensembl)
ADIPOGeneProductENSG00000181092 (Ensembl)
TNF alphaGeneProductENSG00000232810 (Ensembl)
MafAGeneProductENSG00000182759 (Ensembl)
IRSGeneProductENSG00000169047 (Ensembl)
SURF1GeneProductENSG00000148290 (Ensembl)
P13KGeneProductENSG00000141506 (Ensembl)
Ca2+MetaboliteHMDB00464 (HMDB)
SOCSGeneProductENSG00000180008 (Ensembl)
VDCCGeneProductENSG00000141837 (Ensembl)
ERKGeneProductENSG00000100030 (Ensembl)
PDX-1GeneProductENSG00000139515 (Ensembl)
IKKGeneProductENSG00000104365 (Ensembl)
GLUT2GeneProductENSG00000163581 (Ensembl)
JNKGeneProductENSG00000107643 (Ensembl)
PYKGeneProductENSG00000044446 (Ensembl)
mTORGeneProductENSG00000198793 (Ensembl)
ApoptosisPathwayWP254 (WikiPathways)
PRKCZGeneProductENSG00000067606 (Ensembl)
ATPMetaboliteHMDB00538 (HMDB)
PRKCDGeneProductENSG00000163932 (Ensembl)
GlucoseMetaboliteHMDB00122 (HMDB)
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