Differential mitogenic signaling in insulin receptor-deficient fetal pancreatic beta-cells
Authors: C Guillen
M Robledo
M Benito
A M Valverde
P Navarro
Journal: Endocrinology (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Insulin receptor; beta-cell development; signaling system; beta-cell lines; mitogenesis
Affiliations: Institute of Biochemistry/Department of Biochemistry and Molecular Biology, Joint Center Consejo Superior Investigacion Cientifica/Universidad Complutense, School of Pharmacy, Complutense University, Madrid, Spain.

Abstract:  Insulin receptor (IR) may play an essential role in the development of beta-cell mass in the mouse pancreas. To further define the function of this signaling system in beta-cell development, we generated IR-deficient beta-cell lines. Fetal pancreata were dissected from mice harboring a floxed allele of the insulin receptor (IRLoxP) and used to isolate islets. These islets were infected with a retrovirus to express simian virus 40 large T antigen, a strategy for establishing beta-cell lines (beta-IRLoxP). Subsequently, these cells were infected with adenovirus encoding cre recombinase to delete insulin receptor (beta-IR(-/-)). beta-Cells expressed insulin and Pdx-1 mRNA in response to glucose. In beta-IRLoxP beta-cells, p44/p42 MAPK and phosphatidylinositol 3 kinase pathways, mammalian target of rapamycin (mTOR), and p70S(6)K phosphorylation and beta-cell proliferation were stimulated in response to insulin. Wortmannin or PD98059 had no effect on insulin-mediated mTOR/p70S(6)K signaling and the corresponding mitogenic response. However, the presence of both inhibitors totally impaired these signaling pathways and mitogenesis in response to insulin. Rapamycin completely blocked insulin-activated mTOR/p70S(6)K signaling and mitogenesis. Interestingly, in beta-IR(-/-) beta-cells, glucose failed to stimulate phosphatidylinositol 3 kinase activity but induced p44/p42 MAPKs and mTOR/p70S(6)K phosphorylation and beta-cell mitogenesis. PD98059, but not wortmannin, inhibited glucose-induced mTOR/p70S(6)K signaling and mitogenesis in those cells. Finally, rapamycin blocked glucose-mediated mitogenesis of beta-IR(-/-) cells. In conclusion, independently of glucose, insulin can mediate mitogenesis in fetal pancreatic beta-cell lines. However, in the absence of the insulin receptor, glucose induces beta-cell mitogenesis. 

Retracted: No

PubPeer comments:
 Figure 3A and 3B: More similar than expected, could authors check please? ![file] , 
 Thanks to Raphidocelis rotunda for this comment. I have been able to find the original scans and, after checking the documents, these images were added by mistake during the generation of the final version of the manuscript. I send you attached in this message, the images at high resolution of the corresponding blots corresponding to the beta actin of figure 3A and 3B indicated in the comment. These changes do not affect neither the conclusions made by the authors nor the validity of the results of the present article, which has been validated by different authors. ![file] Best regards Carlos , 
 #2 Thanks for your reply.  *These changes do not affect...* -- Does this mean the authors are going to ask for an erratum? , 
 Right panel figure 2A. Much more similar than expected. ![file] ,