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| Status |
Public on Nov 28, 2015 |
| Title |
Drosophila HNF4 promotes glucose-stimulated insulin secretion and increased mitochondrial function in adults [RNA-seq] |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Although mutations in the nuclear receptor HNF4A were identified as the cause of Maturity Onset Diabetes of the Young 1 (MODY1) nearly two decades ago, the mechanisms by which HNF4A regulates glucose homeostasis remain unclear. Here we report that loss of Drosophila HNF4 recapitulates hallmark symptoms of MODY1, including adult-onset hyperglycemia, glucose intolerance and impaired glucose-stimulated insulin secretion (GSIS). These defects are linked to an unexpected role for dHNF4 within mitochondria to directly regulate mtDNA transcription, while also promoting the expression of nuclear genes involved in oxidative phosphorylation (OXPHOS) and Hex-C, a homolog of the MODY2 gene Glucokinase. dHNF4 is required in the fat body and insulin-producing cells to maintain glucose homeostasis by supporting a developmental switch toward OXPHOS and GSIS at the transition to adulthood. These findings establish an animal model for MODY1 and define a developmental reprogramming of metabolism to support the energetic needs of the mature animal.
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| Overall design |
Examination of poly(A)-selected transcripts in dHNF4 mutant adult males versus genetically matched controls.
Control samples - transheterozygotes from precise excisions of P-elements EP2449 and KG08976 (EP/KG) in the w1118 genetic background
dHNF4 mutants - dHNF4∆17/∆33 (transheterozygotes derived from imprecise excisions of P-elements EP2449 and KG08976, respectively)
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| Contributor(s) |
Barry WE, Thummel CS |
| Citation(s) |
27185732 |
| Submission date |
Sep 28, 2015 |
| Last update date |
May 27, 2020 |
| Contact name |
Carl S Thummel |
| Organization name |
University of Utah, School of Medicine
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| Department |
Human Genetics
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| Lab |
Carl Thummel Lab
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| Street address |
15 N 2030 E, Room 5200
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| City |
Salt Lake City |
| State/province |
UT |
| ZIP/Postal code |
84112 |
| Country |
USA |
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| Platforms (1) |
| GPL13304 |
Illumina HiSeq 2000 (Drosophila melanogaster) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE73676 |
Drosophila HNF4 promotes glucose-stimulated insulin secretion and increased mitochondrial function in adults |
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| Relations |
| BioProject |
PRJNA297213 |
| SRA |
SRP064257 |
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