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Transcriptome of pancreas-specific Bmpr1a-deleted islets links to TPH1–5-HT axis
Biology Open
  • Fang-Xu Jiang, The Walter & Eliza Hall Institute of Medical Research,
  • Yuji Mishina, University of Michigan
  • Abdul KMA Baten, Southern Cross University
  • Grant Morahan, University of Western Australia
  • Leonard C Harrison, The Walter & Eliza Hall Institute of Medical Research,
Document Type
Article
Publication Date
1-1-2015
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.
Disciplines
Citation Information

Jiang, FX, Mishina, Y, Baten, AKMA, Morahan, G & Harrison, LC in press, 'Transcriptome of pancreas-specific Bmpr1a-deleted islets links to TPH1–5-HT axis', Biology One.

Article available on Open Access