Differential Mitogenic Signaling in Insulin Receptor-Deficient Fetal Pancreatic β-Cells

C. Guillen, P. Navarro, M. Robledo, A. M. Valverde, M. Benito
2006 Endocrinology  
Purpose of the investigation: 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 have generated IR-deficient beta cell lines. Methods: 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 SV40 large T antigen, a strategy for
more » ... en, a strategy for establishing beta cell lines (β-IRLoxP). Subsequently, these cells were infected with adenovirus encoding cre recombinase to delete insulin receptor (β-IR-/-). Results: Beta cells expressed insulin and Pdx-1 mRNA in response to glucose. In β-IRLoxP beta cells, p44/p42 MAPK and PI 3 kinase pathways, mTOR and p70S 6 K phosphorylation and β-cell proliferation were stimulated in response to insulin. Wortmannin or PD98059 had no effect on insulinmediated mTOR/p70S 6 K signaling and the corresponding mitogenic response. However,
doi:10.1210/en.2005-0831 pmid:16396989 fatcat:im3qtvqty5bltns7iewomttqqi