PERK EIF2AK3 control of pancreatic β cell differentiation and proliferation is required for postnatal glucose homeostasis

Wei Zhang, Daorong Feng, Yulin Li, Kaori Iida, Barbara McGrath, Douglas R. Cavener

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

Mutations in PERK (EIF2AK3) result in permanent neonatal diabetes as well as several other anomalies that underlie the human Wolcott-Rallison syndrome, and these anomalies are mirrored in Perk knockout mice. To identify the cause of diabetes in PERK-deficient mice, we generated a series of tissue- and cell-specific knockouts of the Perk gene and performed a developmental analysis of the progression to overt diabetes. We discovered that PERK is specifically required in the insulin-secreting β cells during the fetal and early neonatal period as a prerequisite for postnatal glucose homeostasis. However, PERK expression in β cells is not required at the adult stage to maintain β cell functions and glucose homeostasis. We show that PERK-deficient mice exhibit severe defects in fetal/neonatal β cell proliferation and differentiation, resulting in low β cell mass, defects in proinsulin trafficking, and abrogation of insulin secretion that culminate in permanent neonatal diabetes.

Original languageEnglish (US)
Pages (from-to)491-497
Number of pages7
JournalCell Metabolism
Volume4
Issue number6
DOIs
StatePublished - Dec 2006
Externally publishedYes

Fingerprint

Cell Differentiation
Homeostasis
Cell Proliferation
Glucose
Proinsulin
Gene Knockout Techniques
Insulin-Secreting Cells
Knockout Mice
Insulin
Mutation

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

PERK EIF2AK3 control of pancreatic β cell differentiation and proliferation is required for postnatal glucose homeostasis. / Zhang, Wei; Feng, Daorong; Li, Yulin; Iida, Kaori; McGrath, Barbara; Cavener, Douglas R.

In: Cell Metabolism, Vol. 4, No. 6, 12.2006, p. 491-497.

Research output: Contribution to journalArticle

Zhang, Wei ; Feng, Daorong ; Li, Yulin ; Iida, Kaori ; McGrath, Barbara ; Cavener, Douglas R. / PERK EIF2AK3 control of pancreatic β cell differentiation and proliferation is required for postnatal glucose homeostasis. In: Cell Metabolism. 2006 ; Vol. 4, No. 6. pp. 491-497.
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