RGD Reference Report - Pancreatic islet-specific overexpression of Reg3beta protein induced the expression of pro-islet genes and protected the mice against streptozotocin-induced diabetes mellitus. - 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   new 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

Pancreatic islet-specific overexpression of Reg3beta protein induced the expression of pro-islet genes and protected the mice against streptozotocin-induced diabetes mellitus.

Authors: Xiong, X  Wang, X  Li, B  Chowdhury, S  Lu, Y  Srikant, CB  Ning, G  Liu, JL 
Citation: Xiong X, etal., Am J Physiol Endocrinol Metab. 2011 Apr;300(4):E669-80. doi: 10.1152/ajpendo.00600.2010. Epub 2011 Jan 18.
RGD ID: 9831432
Pubmed: PMID:21245462   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00600.2010   (Journal Full-text)

Reg family proteins have been implicated in islet beta-cell proliferation, survival, and regeneration. The expression of Reg3beta (pancreatitis-associated protein) is highly induced in experimental diabetes and acute pancreatitis, but its precise role has not been established. Through knockout studies, this protein was shown to be mitogenic, antiapoptotic, and anti-inflammatory in the liver and pancreatic acinars. To test whether it can promote islet cell growth or survival against experimental damage, we developed beta-cell-specific overexpression using rat insulin I promoter, evaluated the changes in normal islet function, gene expression profile, and the response to streptozotocin-induced diabetes. Significant and specific overexpression of Reg3beta was achieved in the pancreatic islets of RIP-I/Reg3beta mice, which exhibited normal islet histology, beta-cell mass, and in vivo and in vitro insulin secretion in response to high glucose yet were slightly hyperglycemic and low in islet GLUT2 level. Upon streptozotocin treatment, in contrast to wild-type littermates that became hyperglycemic in 3 days and lost 15% of their weight, RIP-I/Reg3beta mice were significantly protected from hyperglycemia and weight loss. To identify specific targets affected by Reg3beta overexpression, a whole genome DNA microarray on islet RNA isolated from the transgenic mice revealed more than 45 genes significantly either up- or downregulated. Among them, islet-protective osteopontin/SPP1 and acute responsive nuclear protein p8/NUPR1 were significantly induced, a result further confirmed by real-time PCR, Western blots, and immunohistochemistry. Our results suggest that Reg3beta is unlikely an islet growth factor but a putative protector that prevents streptozotocin-induced damage by inducing the expression of specific genes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus susceptibilityISOReg3b (Mus musculus)9831432; 9831432 RGD 
Experimental Diabetes Mellitus susceptibilityIMP 9831432 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Reg3b  (regenerating family member 3 beta)

Genes (Mus musculus)
Reg3b  (regenerating islet-derived 3 beta)

Genes (Homo sapiens)
REG3A  (regenerating family member 3 alpha)


Additional Information