The diabetes gene Hhex maintains δ-cell differentiation and islet function

J Zhang, LB McKenna, CW Bogue… - Genes & …, 2014 - genesdev.cshlp.org
J Zhang, LB McKenna, CW Bogue, KH Kaestner
Genes & development, 2014genesdev.cshlp.org
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 …
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.
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