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| Status |
Public on May 20, 2022 |
| Title |
A critical role of the mechanosensor PIEZO1 in glucose-induced insulin secretion in pancreatic β-cells |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
PIEZO1 is a mechanosensitive ion channel involved in the regulation of a diverse range of physiological responses. We examined the role of the mechanosensor ion channel PIEZO1 in glucose-induced insulin secretion in pancreatic β-cells. PIEZO1 expression is elevated in β-cells from human donors with type-2 diabetes (T2D) and a rodent T2D model (db/db 48 mouse). Silencing of Piezo1 inhibits glucose-induced Ca2+ signaling and insulin secretion. PIEZO1 translocates from the cytosol and plasmalemma into the nucleus in cells cultured at high glucose, experimental conditions emulating diabetes. The translocation of PIEZO1 into the nucleus in response to hyperglycemia suggests that PIEZO1 might be involved in transcriptional control in addition to serving as a mechanosensor in the plasma membrane. To address this, we performed mRNA sequencing in INS-1 832/13 cells to determine which genes are regulated by Piezo channels. Overall, we found 3292, 1656, and 1920 genes were significantly differentially expressed after silencing Piezo1, Piezo2, or both genes (adj.p-value < 0.05). Among these, the expression of the gene encoding cocaine- and amphetamine-regulated transcript (Cartpt) was increased >15-fold. We confirmed this effect by qPCR, which indicated a corresponding stimulation of expression. In insulin-secreting INS-1 832/13 cells, Cart has been reported to influence the expression and release of insulin. Thus, the impact of PIEZO1 on β-cell function may not be limited to electrical excitability but these changes are likely to operate on a slower timescale than the acute/electrical effects.
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| Overall design |
Examination of mRNA profiles of untreated, treated with non-targeting siRNA, Piezo1-silenced, Piezo2-silenced, Piezo1 and Piezo2 silenced INS-1 cells (4 replicates/5 conditions)
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| Contributor(s) |
Karagiannopoulos A, Ye Y, Zhang E, Renström E |
| Citation(s) |
35869052 |
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| Submission date |
Feb 25, 2022 |
| Last update date |
Aug 03, 2022 |
| Contact name |
Lena Eliasson |
| E-mail(s) |
lena.eliasson@med.lu.se
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| Organization name |
Lund University Diabetes Centre
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| Lab |
Unit of Islet Cell Exocytosis
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| Street address |
Jan Waldenströms gata 35
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| City |
Malmö |
| ZIP/Postal code |
20502 |
| Country |
Sweden |
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| Platforms (1) |
| GPL20084 |
Illumina NextSeq 500 (Rattus norvegicus) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA810375 |
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