Disrupted glucose homeostasis and glucagon and insulin secretion defects in Robo KO mice

The axon guidance proteins, Roundabout (Robo) receptors play a critical role in morphogenesis of the islets of Langerhans. Mice with a beta cell-selective deletion of Robo (Robo beta KO), show severely disrupted spatial architecture of their islets, without defects in beta cell differentiation or maturity. We have recently shown that Robo beta KO mice have reduced synchronous glucose-stimulated beta cell calcium oscillations in their islets in vivo, likely disrupting their pulsatile insulin secretion. Here, we analyze whole-body metabolic regulation in Robo beta KO mice. We show that Robo beta KO mice have mild defects in glucose homeostasis, and altered glucagon and insulin secretion. However, we did not observe any severe whole-body glucoregulatory phenotype following the disruption of islet architecture in Robo beta KO. Our data suggest that islet architecture plays only a mild role in overall glucoregulation.