Transcription factor-7-like 2 () gene acts downstream of the / kinase to control mTOR signaling, β cell growth, and insulin secretion.

Variants in the transcription factor-7-like 2 (/) gene, involved in Wnt signaling, are associated with type 2 diabetes. Loss of selectively from the β cell in mice has previously been shown to cause glucose intolerance and to lower β cell mass. Deletion of the tumor suppressor liver kinase B1 (LKB1/STK11) leads to β cell hyperplasia and enhanced glucose-stimulated insulin secretion, providing a convenient genetic model for increased β cell growth and function. The aim of this study was to explore the possibility that may be required for the effects of deletion on insulin secretion in the mouse β cell. Mice bearing floxed and/or alleles were bred with knockin mice bearing recombinase inserted at the locus (), allowing highly β cell-selective deletion of either or both genes. Oral glucose tolerance was unchanged by the further deletion of a single allele in these cells. By contrast, mice lacking both alleles on this background showed improved oral glucose tolerance and insulin secretion and compared with mice lacking a single allele. Biallelic deletion also enhanced β cell proliferation, increased β cell mass, and caused changes in polarity as revealed by the "rosette-like" arrangement of β cells. deletion also increased signaling by mammalian target of rapamycin (mTOR), augmenting phospho-ribosomal S6 levels. We identified a novel signaling mechanism through which a modifier gene, , lies on a pathway through which LKB1 acts in the β cell to restrict insulin secretion.