Date of Award
pancreas development, diabetes mellitus, pancreatic beta cells, transmembrane protein 27
The signals and the molecular mechanisms that regulate the replication of terminally differentiated Î² cells are unclear. In this thesis I report the identification of a gene encoding transmembrane protein 27 (TMEM27) in pancreatic Î² cells. Expression of Tmem27 is reduced in Tcf1â€“/â€“ mice, which exhibit defects in proliferation, and is increased in islets of ob/ob, db/db and aP2- Srebp-1c transgenic 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 Î² cells in the mature pancreas. Biochemical characterization revealed that the Tmem27 exists as a dimer and that its extracellular domain is glycosylated, cleaved and shed from the plasma membrane. The cleavage process of Tmem27 is Î² cell-specific and does not occur in other cell types. Overexpression of full-length Tmem27, but not the truncated or soluble protein, 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 Î² cells exhibit increased Î² cell mass compared to their control littermates. The following results identify a novel pancreatic Î² cell-shed protein that regulates cell growth of pancreatic islets.
Akpinar, Pinar, "TMEM27: A Cleaved and Shed Plasma Membrane Protein That Stimulates Pancreatic Beta Cell Proliferation" (2006). Student Theses and Dissertations. 2.