Endocrine Abstracts

Beta-cell hyperplasia is an important adaptive mechanisms to maintain normoglycemia during physiological growth and in obesity. Increasing evidence suggests that the β-cell mass is dynamic and that increase demands on insulin secretion in insulin resistance and pregnancy can lead to rapid and marked changes in the β-cell mass. The mass of β-cells is governed by the balance of ß cell growth (replication) and by β-cell death (apoptosis). The molecular basis of the factors that control β-cell mass remain elusive. We have identified a gene encoding transmembrane protein 27 (TMEM27) in pancreatic β-cells. Expression of TMEM27 is reduced in Hnf1β^−/− mice, which exhibit defects in proliferation, and is increased islets of ob/ob mice with marked hypertrophy of the endocrine pancreas. TMEM27 is expressed in hormone positive cells at early stages of pancreas development and becomes restricted to pancreatic β-cells in the mature pancreas. Biochemical characterization revealed that the TMEM exists as a dimer and that its extracellular domain is glycosylated, cleaved and secreted. The cleavage process of TMEM27 is β-cell-specific and does not occur in other cell types. Overexpression of TMEM27 in MIN6 cells leads to increased thymidine incorporation, whereas silencing of TMEM27 using RNAi results in a reduction of cell replication. Furthermore, transgenic mice with increased expression of TMEM27 in pancreatic β-cells exhibit increased islet mass compared to their control littermates. Our results identify a novel pancreatic β-cell secreted protein that regulates cell growth in pancreatic islets.