RGD Reference Report - Lactogens promote beta cell survival through JAK2/STAT5 activation and Bcl-XL upregulation. - Rat Genome Database

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Lactogens promote beta cell survival through JAK2/STAT5 activation and Bcl-XL upregulation.

Authors: Fujinaka, Y  Takane, K  Yamashita, H  Vasavada, RC 
Citation: Fujinaka Y, etal., J Biol Chem. 2007 Oct 19;282(42):30707-17. Epub 2007 Aug 29.
RGD ID: 1643490
Pubmed: PMID:17728251   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M702607200   (Journal Full-text)

One of the goals in the treatment for diabetes is to enhance pancreatic beta cell function, proliferation, and survival. This study explores the role of lactogenic hormones, prolactin (PRL) and placental lactogen (PL), in beta cell survival. We have previously shown that transgenic mice expressing mouse placental lactogen-1 (mPL1) in beta cells under the rat insulin II promoter (RIP) are resistant to the diabetogenic and cytotoxic effects of streptozotocin (STZ) in vivo. The current study demonstrates that lactogens protect rat insulinoma (INS-1) cells and primary mouse beta cells against two distinct beta cell death inducers, STZ and dexamethasone (DEX), in vitro. Further, we identify the mechanism through which lactogens protect beta cells against DEX-induced death. The signaling pathway mediating this protective effect is the janus-activated-kinase-2/signal transducer and activator of transcription-5 (JAK2/STAT5) pathway. This is demonstrated in INS-1 cells and primary mouse beta cells using three separate approaches, pharmacological inhibitors, JAK2-specific siRNAs and a dominant-negative STAT5 mutant. Furthermore, lactogens specifically and significantly increase the anti-apoptotic protein Bcl-XL in insulinoma cells and mouse islets. Bcl-XL-specific siRNA significantly inhibits lactogen-mediated protection against DEX-induced beta cell death. We believe this is the first direct demonstration of lactogens mediating their protective effect through the JAK2/STAT5 pathway in the beta cell and through Bcl-XL in any cell type.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to peptide hormone  IEP 1643490 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bcl2l1  (Bcl2-like 1)


Additional Information