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Endocrinology. 2018 Feb 1;159(2):1062-1073. doi: 10.1210/en.2017-00685.

GRP94 Is an Essential Regulator of Pancreatic β-Cell Development, Mass, and Function in Male Mice.

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Department of Surgery, Medical University of South Carolina, Charleston, South Carolina.
Department of Medicine, Tulane University, New Orleans, Louisiana.
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee.
Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina.
Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina.


Deficiencies in pancreatic β-cell mass contribute to both type 1 and type 2 diabetes. We investigated the role of the glucose-regulated protein (GRP) 94, an endoplasmic reticulum protein abundantly expressed in the pancreatic acini and islets, in β-cell development, survival, and function. We used a conditional knockout (KO) mouse in which the GRP94 gene, Hsp90b1, was specifically deleted in pancreatic and duodenal homeobox 1 (Pdx1)-expressing cells. These Hsp90b1 flox/flox;Pdx1Cre KO mice exhibited pancreatic hypoplasia at embryonic day (E) 16.5 to E18.5 and had significantly reduced β-cell mass at 4 weeks after birth. Further mechanistic studies showed that deletion of GRP94 reduced β-cell proliferation with increased cell apoptosis in both Pdx1+ endocrine progenitor cells and differentiated β cells. Although Hsp90b1 flox/flox;Pdx1Cre KO mice remained euglycemic at 8 weeks of age, they exhibited impaired glucose tolerance. In aggregate, these findings indicate that GRP94 is an essential regulator of pancreatic β-cell development, mass, and function.

[Available on 2019-02-01]
[Indexed for MEDLINE]

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