Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Pancreas-specific Deletion of Bmpr1a Impairs Glucose Homeostasis Linked to Overexpression of Tph1 (#107)

Fang-Xu Jiang 1
  1. University of Western Australia, Perth, WA, Australia

Despite having diverse roles in multi-organs temporal-spatially, bone morphogenetic protein (BMP) signaling on pancreas development and function is poorly defined. We here report that pancreas-specific deletion of its receptor Bmpr1a (Panc cKO) reduced expression of the key cell-cell interaction molecule E-cadherin in developing endocrine cells. Importantly, these Panc cKO mice had impaired glucose homeostasis at 3 months, and were more severely affected at 12 months of age. These mice displayed spontaneous glucose intolerance and had lower fasting blood insulin concentrations, with reduced expression of several key regulators of insulin secretion and function. Crucially, bioinformatics analyses of transcriptomic profiling datasets of islets from homozygous Panc cKO mice revealed a striking over-expression of the tryptophan hydroxylase 1 gene (Tph1), encoding the rate-limiting enzyme for the production of 5-hydroxytryptamine (5-HT). Chronic excess 5-HT inhibited insulin secretion by b cells. Hence we conclude that BMPR1A regulates glucose homeostasis by suppressing the Tph-5-HT axis in b cells.