Type II diabetes mellitus (Homo sapiens)

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Ca 2+ dependent Pancreatic beta cell transient hyperglycemia hyperinsulinism Insulin Resistance Adipotocyte, heptocyte, skeletal muscle cell Adipoctokine signaling pathway ROS Maturity onset diabetes of the young +ps (serine phosphorylation) obesity Glucose ( hyperglycemia) Impaired Insulin Secretion K+ DNA Obesity glycation, hexosamine pathway, respiratory chain Adipocytokine Signaling Pathway Type II diabetes mellitus Prevention of membrane depolarization Insulin signaling pathway FFA +py (tyrosine phosphorylation) Kir6.2 TNF alpha INSR ERK MafA GLUT4 GLUT2 PRKCZ INS P13K Apoptosis ADIPO PYK Ca2+ Pyruvate GK VDCC ATP INS SOCS JNK IRS Glucose mTOR PDX-1 PRKCD SURF1 IRS JNK IKK Name: Type II diabetes mellitus License: CC BY 2.0 Last Modified: 2/22/2013 Organism: Homo sapiens


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.

Source: KEGG

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Ontology Terms

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Bibliography

  1. Henquin JC; ''Triggering and amplifying pathways of regulation of insulin secretion by glucose.''; Diabetes, 2000 PubMed
  2. Chandra J, Zhivotovsky B, Zaitsev S, Juntti-Berggren L, Berggren PO, Orrenius S; ''Role of apoptosis in pancreatic beta-cell death in diabetes.''; Diabetes, 2001 PubMed
  3. Gual P, Le Marchand-Brustel Y, Tanti JF; ''Positive and negative regulation of insulin signaling through IRS-1 phosphorylation.''; Biochimie, 2005 PubMed
  4. Kaneto H, Matsuoka TA, Nakatani Y, Kawamori D, Miyatsuka T, Matsuhisa M, Yamasaki Y; ''Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes.''; J Mol Med (Berl), 2005 PubMed

History

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RevisionActionTimeUserComment
94959view 03:10, 20 October 2017DeSlAdded lit. references
94958view 02:44, 20 October 2017DeSlConnected all lines that I could
81779view 12:00, 26 August 2015KhanspersModified description
81778view 11:58, 26 August 2015KhanspersModified description
72094view 14:35, 24 October 2013Mkutmonupdated datasource for "Apoptosis"
67730view 04:55, 26 June 2013DdiglesOntology Term : 'type 2 diabetes mellitus pathway' added !
63481view 11:29, 10 May 2013AlexanderPicoFixed Xref for PYK
63274view 00:16, 9 May 2013EveloPeriodical save, work in progress
59217view 13:13, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
45036view 11:50, 6 October 2011KhanspersOntology Term : 'pancreatic beta cell' added !
45034view 11:49, 6 October 2011KhanspersOntology Term : 'hyperglycemia' added !
45032view 11:47, 6 October 2011KhanspersOntology Term : 'DOID:9351' removed !
45031view 11:47, 6 October 2011KhanspersOntology Term : 'type 2 diabetes mellitus' added !
45030view 11:47, 6 October 2011KhanspersOntology Term : 'Diabetes' added !
41223view 16:45, 1 March 2011MaintBotRemoved redundant pathway information and comments
38693view 11:35, 23 September 2010KhanspersChanged layout, connected nodes, added metabolites, added pathway links, fixed arrows
38692view 11:26, 23 September 2010KhanspersPeriodical save, work in progress
38690view 11:25, 23 September 2010Khanspersperiodical save
38312view 15:45, 31 August 2010KhanspersChanged OrganA to Oval
38145view 12:00, 17 August 2010KhanspersModified categories
37822view 03:08, 6 July 2010AnkuPeriodical save, work in progress
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37819view 02:34, 6 July 2010AnkuPeriodical save, work in progress
37813view 08:05, 5 July 2010AnkuModified description
37812view 08:04, 5 July 2010Ankudiabetes type II
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37798view 04:11, 5 July 2010Ankutype II
37797view 04:04, 5 July 2010AnkuPeriodical save, work in progress
37796view 03:44, 5 July 2010AnkuNew pathway

External references

DataNodes

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

Annotated Interactions

<cite>No annotated interactions</cite>