title: Transcriptome of pancreas-specific Bmpr1a-deleted islets links to TPH1-5-HT axis.
abstract: Bone morphogenetic protein (BMP) signaling is crucial for the development and function of numerous organs, but its role on the function of pancreatic islets is not completely clear. To explore this question, we applied the high throughput transcriptomic analyses on the islets isolated from mice with a pancreas-specific deletion of the gene, Bmpr1a, encoding the type 1a BMP receptor. Consistently, these pBmpr1aKO mice had impaired glucose homeostasis at 3 months, and were more severely affected at 12 months of age. These had lower fasting blood insulin concentrations, with reduced expression of several key regulators of β-cell function. Importantly, transcriptomic profiling of 3-month pBmpr1aKO islets and bioinformatic analyses revealed abnormal expression of 203 metabolic genes. Critically among these, the tryptophan hydroxylase 1 gene (Tph1), encoding the rate-limiting enzyme for the production of 5-hydroxytryptamine (5-HT) was the highest over-expressed one. 5-HT is an important regulator of insulin secretion from β cells. Treatment with excess 5-HT inhibited this secretion. Thus our transcriptomic analysis links two highly conserved molecular pathways the BMP signaling and the TPH1-5-HT axis on glucose homeostasis.
authors.affiliation: The Walter & Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia Harry Perkins Institute of Medical Research, Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009, Australia fangxu.jiang@uwa.edu.au.
authors.forename: Fang-Xu
authors.initials: FX
authors.lastname: Jiang
authors.affiliation: Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishina
authors.affiliation: Harry Perkins Institute of Medical Research, Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors.forename: Akma
authors.initials: A
authors.lastname: Baten
authors.affiliation: Harry Perkins Institute of Medical Research, Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
authors.affiliation: The Walter & Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Harrison
keywords: BMPR1A; Glucose homeostasis; Tph1; Transcriptome