RGD Reference Report - Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in islets. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in islets.

Authors: Zhou, J  Livak, MF  Bernier, M  Muller, DC  Carlson, OD  Elahi, D  Maudsley, S  Egan, JM 
Citation: Zhou J, etal., Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E538-47. Epub 2007 May 15.
RGD ID: 2312603
Pubmed: PMID:17505054   (View Abstract at PubMed)
PMCID: PMC2640485   (View Article at PubMed Central)
DOI: DOI:10.1152/ajpendo.00070.2007   (Journal Full-text)

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that has a potent stimulatory effect on insulin release under conditions of normal glucose tolerance. However, its insulinotropic effect is reduced or even absent entirely in type 2 diabetic patients. In this study, we addressed the role of glucose concentration in the diabetic range of >or=11 mM, i.e., hyperglycemia per se, as a cause of the lack of response to GIP. Culturing rat and human pancreatic islets in >or=11 mM glucose for up to 24 h resulted in prevention of GIP-mediated intracellular cAMP increase compared with culturing in 5 mM glucose. Western blot analysis revealed a selective 67 +/- 2% (rat) and 60 +/- 8% (human) decrease of GIP-R expression in islets exposed to >or=11 mM glucose compared with 5 mM glucose (P < 0.001). We further immunoprecipitated GIP-R from islets and found that GIP-R was targeted for ubiquitination in a glucose- and time-dependent manner. Downregulation of GIP-R was rescued by treating isolated islets with proteasomal inhibitors lactacystin and MG-132, and the islets were once again capable of increasing intracellular cAMP levels in response to GIP. These results suggest that the GIP-R is ubiquitated, resulting in downregulation of the actions of GIP.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GIPRHumanhyperglycemia  ISOGipr (Rattus norvegicus)protein:decreased expression:pancreatic islet (rat)RGD 
GiprRathyperglycemia  IEP protein:decreased expression:pancreatic islet (rat)RGD 
GiprMousehyperglycemia  ISOGipr (Rattus norvegicus)protein:decreased expression:pancreatic islet (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gipr  (gastric inhibitory polypeptide receptor)

Genes (Mus musculus)
Gipr  (gastric inhibitory polypeptide receptor)

Genes (Homo sapiens)
GIPR  (gastric inhibitory polypeptide receptor)


Additional Information