Transcriptome of pancreas-specific Bmpr1a-deleted islets links to TPH1-5-HT axis

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...

Full description

Saved in:
Bibliographic Details
Published in:Biology open 2015-08, Vol.4 (8), p.1016-1023
Main Authors: Jiang, Fang-Xu, Mishina, Yuji, Baten, Akma, Morahan, Grant, Harrison, Leonard C
Format: Article
Language:English
Subjects:
Beta cells
BMPR1A
Bone morphogenetic proteins
Gene deletion
Gene expression
Glucose
Glucose homeostasis
Homeostasis
Insulin
Insulin secretion
Pancreas
Secretion
Signaling
Tph1
Transcriptome
Transcriptomes
Transcriptomics
Tryptophan
Tryptophan hydroxylase
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2046-6390
2046-6390
DOI:10.1242/bio.011858