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| Status |
Public on Apr 25, 2018 |
| Title |
The role of CFTR in islet function |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cystic fibrosis (CF)-related diabetes (CFRD) is an increasingly common and devastating comorbidity of CF, affecting ~35% of adults with CF. However, the underlying causes of CFRD are unclear. Here, we examined cystic fibrosis transmembrane conductance regulator (CFTR) islet expression and whether the CFTR participates in islet endocrine cell function using murine models of b cell CFTR deletion, and normal and CF human pancreas and islets. Specific deletion of CFTR from murine b cells did not affect b cell function. In human islets, CFTR mRNA was minimally expressed, and CFTR protein/electrical activity was not detected. Isolated CF/CFRD islets demonstrated appropriate insulin and glucagon secretion with few changes in key islet-regulatory transcripts. Furthermore, ~65% of b cell area was lost in CF donors, compounded by pancreatic remodeling and immune infiltration of the islet. These results indicate that CFRD is not caused by intrinsic islet dysfunction from CFTR mutation, but rather, by b cell loss and intra-islet inflammation in the setting of a complex pleiotropic disease
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| Overall design |
Human samples 3351-ACP-005, -0017, -0020, -0027, -0036 are isolated islets from normal healthy individuals. 3362-ACP-0011, -0012,-0013,-0014,-0015 are isolated from individuals with cystic fibrosis. 12 samples from mouse.
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| Contributor(s) |
Hart NJ, Powers AC |
| Citation(s) |
29669939 |
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| Submission date |
Feb 21, 2018 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Nathaniel Hart |
| E-mail(s) |
nathaniel.j.hart@vanderbilt.edu
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| Organization name |
Vanderbilt University Medical Center
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| Department |
Medicine
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| Lab |
Alvin Powers
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| Street address |
7465 Medical Research Building IV, 2215 Garland Ave.
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| City |
Nashville |
| State/province |
TN |
| ZIP/Postal code |
37232-0475 |
| Country |
USA |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA434833 |
| SRA |
SRP133211 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE110935_NEV_Human_RNAseq.xlsx |
5.7 Mb |
(ftp)(http) |
XLSX |
| GSE110935_NEV_Mouse_RNAseq.xlsx |
5.1 Mb |
(ftp)(http) |
XLSX |
| GSE110935_Normalized_expression_values_mouse_3632ACP.xlsx |
9.0 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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