title: The diabetes gene Hhex maintains δ-cell differentiation and islet function.
abstract: The homeodomain transcription factor HHEX (hematopoietically expressed homeobox) has been repeatedly linked to type 2 diabetes mellitus (T2DM) using genome-wide association studies. We report here that within the adult endocrine pancreas, Hhex is selectively expressed in the somatostatin-secreting δ cell. Using two mouse models with Hhex deficiency in the endocrine pancreas, we show that Hhex is required for δ-cell differentiation. Decreased somatostatin levels in Hhex-deficient islets cause disrupted paracrine inhibition of insulin release from β cells. These findings identify Hhex as the first transcriptional regulator specifically required for islet δ cells and suggest compromised paracrine control as a contributor to T2DM.
authors.affiliation: Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: McKenna
authors.forename: Clifford W
authors.initials: CW
authors.lastname: Bogue
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019899:Paracrine Communication / Q000502:physiology; D019864:Somatostatin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors
keywords: diabetes; pancreatic islet; somatostatin; transcription factors; δ cell
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