Disrupted glucose homeostasis and glucagon and insulin secretion defects in Robo βKO mice.

The axon guidance proteins, Roundabout (Robo) receptors play a critical role in morphogenesis of the islets of Langerhans. Mice with a β cell-selective deletion of Robo (Robo βKO), show severely disrupted spatial architecture of their islets, without defects in β cell differentiation or maturity. We have recently shown that Robo βKO mice have reduced synchronous glucose-stimulated β cell calcium oscillations in their islets in vivo, likely disrupting their pulsatile insulin secretion. Here, we analyze whole-body metabolic regulation in Robo βKO mice. We show that Robo βKO 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 βKO. Our data suggest that islet architecture plays only a mild role in overall glucoregulation.