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| Status |
Public on Aug 09, 2021 |
| Title |
Islet Sympathetic Innervation and Islet Neuropathology in Patients with Type 1 Diabetes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Dysregulation of glucagon secretion in type 1 diabetes (T1D) involves hypersecretion during postprandial states, but insufficient secretion during hypoglycemia. The sympathetic nervous system regulates glucagon secretion. To investigate islet sympathetic innervation in T1D, sympathetic tyrosine hydroxylase (TH) axons were analyzed in control non-diabetic organ donors, non-diabetic islet autoantibody-positive individuals (AAb), and age-matched persons with T1D. Islet TH axon numbers and density were significantly decreased in AAb compared to T1D with no significant differences observed in exocrine TH axon volume or lengths between groups. TH axons were in close approximation to islet α-cells in T1D individuals with long-standing diabetes. Islet RNA-sequencing and qRT-PCR analyses identified significant alterations in noradrenalin degradation, α-adrenergic signaling, cardiac b-adrenergic signaling, catecholamine biosynthesis, and additional neuropathology pathways. The close approximation of TH axons at islet α-cells supports a model for sympathetic efferent neurons directly regulating glucagon secretion. Sympathetic islet innervation and intrinsic adrenergic signaling pathways could be novel targets for improving glucagon secretion in T1D.
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| Overall design |
Laser microdissected islets from pancreas organ donors were analyzed by RNA-sequencing and bioinformatics to determine differentially regulated genes.
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| Contributor(s) |
Campbell-Thomson M, Butterworth EA, Boatwright JL, Nair MA, Nasif LH, Nasif K, Revell AY, Riva A, Mathews CE, Gerling IC, Schatz DA, Atkinson MA |
| Citation(s) |
33753784 |
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| Submission date |
Aug 09, 2021 |
| Last update date |
Aug 10, 2021 |
| Contact name |
Alberto Riva |
| E-mail(s) |
ariva@ufl.edu
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| Organization name |
University of Florida
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| Department |
ICBR
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| Lab |
Bioinformatics Core
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| Street address |
2033 Mowry Rd
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| City |
Gainesville |
| State/province |
FL |
| ZIP/Postal code |
32605 |
| Country |
USA |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA752997 |
| SRA |
SRP331606 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE181674_AAb-ND_core_analysis.xls.gz |
14.8 Kb |
(ftp)(http) |
XLS |
| GSE181674_AAb-T1D_core_analysis.xls.gz |
16.3 Kb |
(ftp)(http) |
XLS |
| GSE181674_RNAseq-counts.xlsx |
4.2 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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