Diabetes is a chronic disease caused by the loss or dysfunction of the insulin-producing β-cells in the pancreas. To date, much of our knowledge about β-cells in humans comes from studying rare monogenic forms of diabetes. Importantly, the majority of mutations so far associated to monogenic diabetes are in genes that exert a regulatory role in pancreatic development and/or β-cell function. Thus, the identification and study of novel mutations open an unprecedented window into human pancreatic development. In this review, we summarize major advances in the genetic dissection of different types of monogenic diabetes and the insights gained from a developmental perspective. We highlight future challenges to bridge the gap between the fast accumulation of genetic data through next-generation sequencing and the need of functional insights into disease mechanisms. Lastly, we discuss the relevance and advantages of studying candidate gene variants in vivo using the Xenopus as model system.
Copyright © 2016. Published by Elsevier Ltd.