Northwestern University Feinberg School of Medicine

Beatriz Sosa-Pineda Lab

Prox1 Role in Glucose Homeostasis

GWAS results identified single nucleotide polymorphisms (SNPs) in regulatory regions of human PROX1 that correlate with diabetes predisposition. We recently reported that Prox1 overexpression in immature b-cells (A) decreases proliferation (B), reduces pathways involved with FGF signaling (C) and maturation (D) and promotes diabetes, in transgenic mice. We will use in vivo and in vitro approaches to investigate the functional relevance of the former SNIPS on PROX1 expression and their specific effect on glucose homeostasis. Also, we will explore if some of the pathway components identified in our transgenic mouse model are required for the expansion or function of b-cells.

High Prox1 expression in beta cells reduces proliferation and pathways associated with FGF signaling and maturation, and causes diabetes.

A

prox1 and insulin

B

glucagon and insulin

C

Reactome FRS2 mediated cascade

D

Reactome beta cell development