Unknown,Transcriptomics,Genomics,Proteomics

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Prox1 downregulation is a prerequisite for the maturation and expansion of postnatal murine beta cells

ABSTRACT: Alterations in the expression of key transcription factors can be harmful for pancreatic beta cell homeostasis and could lead to diabetes. This study uncovered that Prox1 overexpression obstructs beta cell maturation and results in severe hyperglycemia. The function of β-cells is key for glucose homeostasis because they supply insulin to the entire body. Genetic or metabolic conditions that disrupt the complex physiology of β-cells can lead to diabetes mellitus, a prevalent life-threatening disease. Here we investigated whether sustained Prox1 expression is incompatible with β-cell development using a transgenic mouse approach, and report that β-cell maturation is drastically impaired in the presence of high levels of Prox1. We used microarrays to identify gene expression profiles and pathways that are differentially activated when Prox1 is overexpressed in murine pancreatic beta cells.

ORGANISM(S): Mus musculus

SUBMITTER: Geoffrey Neale 

PROVIDER: E-GEOD-68133 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Lack of Prox1 Downregulation Disrupts the Expansion and Maturation of Postnatal Murine β-Cells.

Paul Leena L   Walker Emily M EM   Drosos Yiannis Y   Cyphert Holly A HA   Neale Geoffrey G   Stein Roland R   South Jack J   Grosveld Gerard G   Herrera Pedro L PL   Sosa-Pineda Beatriz B  

Diabetes 20151202 3

Transcription factor expression fluctuates during β-cell ontogeny, and disruptions in this pattern can affect the development or function of those cells. Here we uncovered that murine endocrine pancreatic progenitors express high levels of the homeodomain transcription factor Prox1, whereas both immature and mature β-cells scarcely express this protein. We also investigated if sustained Prox1 expression is incompatible with β-cell development or maintenance using transgenic mouse approaches. We  ...[more]

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