Human islets exposed to conditions that induce or inhibit calcium signaling
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PROVIDER: PRJNA806952 | ENA |
REPOSITORIES: ENA
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Project description:Pancreatic islets depend on cytosolic calcium to trigger the secretion of glucoregulatory hormones and the transcriptional regulation of genes important for islet response to stimuli. To date, there has not been an attempt to profile calcium-regulated gene expression in all islet cell types. To address this, we generated a large single cell transcriptomic dataset from healthy human islets exposed to conditions that would acutely induce or inhibit intracellular calcium signaling, while preserving biological heterogeneity. Our aim was to use this dataset to identify acutely calcium-regulated genes in each islet cell type, while simulataneously exploring markers of islet heterogeneity.
2022-06-17 | GSE196715 | GEO
Project description:Pulsatility is important to islet function. As islets mature into fully developed insulin-secreting micro-organs, their ability to produce oscillatory intracellular calcium ([Ca2+]i) patterns in response to glucose also matures. In this study, we measured [Ca2+]i using fluorescence imaging to characterize oscillations from neonatal mice on postnatal (PN) days 0, 4, and 12 in comparison to adult islets. Under substimulatory (3-mM) glucose levels, [Ca2+]i was low and quiescent for adult islets as expected, as well as for PN day 12 islets. In contrast, one-third of islets on PN day 0 and 4 displayed robust [Ca2+]i oscillations in low glucose. In stimulatory glucose (11 mM) conditions, oscillations were present on all neonatal days but differed from patterns in adults. By PN day 12, [Ca2+]i oscillations were approaching characteristics of fully developed islets. The immature response pattern of neonatal islets was due, at least in part, to differences in adenosine 5'-triphosphate (ATP)-sensitive K+-channel activity estimated by [Ca2+]i responses to KATP channel agents diazoxide and tolbutamide. Neonatal [Ca2+]i patterns were also strikingly similar to patterns observed in mature islets exposed to hyperglycemic conditions (20 mM glucose for 48 hours): elevated [Ca2+]i and oscillations in low glucose along with reduced pulse mass in high glucose. Since a hallmark of diabetic islets is dedifferentiation, we propose that diabetic islets display features of "reverse maturation," demonstrating similar [Ca2+]i dynamics as neonatal islets. Pulsatility is thus an important emergent feature of neonatal islets. Our findings may provide insight into reversing β-cell dedifferentiation and to producing better functioning β cells from pluripotent stem cells.
| S-EPMC9186310 | biostudies-literature
Project description:We have used RNA-seq to identify transcripts expressed in human islets harboring beta cells transduced to overexpress STX4 and induce chemokine ligand by adenoviral transduction
2019-03-01 | GSE120378 | GEO
Project description:Lorcaserin is a serotonergic agonist specific to the 5-hydroxytryptamine 2c receptor (5-HT2CR) that is FDA approved for the long-term management of obesity with or without at least one weight-related comorbidity. Lorcaserin can restrain patients' appetite and improve insulin sensitivity and hyperinsulinemia mainly through activating 5-HT2CR in the hypothalamus. It is known that the mCPP, a kind of 5-HT2CR agonist, decreases plasma insulin concentration in mice and previous research in our laboratory found that mCPP inhibited glucose-stimulated insulin secretion (GSIS) by activating 5-HT2CR on the β cells. However, the effect of lorcaserin on GSIS of pancreatic β cell has not been studied so far. The present study found that 5-HT2CR was expressed in both mouse pancreatic β cells and β-cell-derived MIN6 cells. Dose-dependent activation of 5-HT2CR by lorcaserin suppressed GSIS and SB242084 or knockdown of 5-HT2CR abolished lorcaserin's effect in vitro. Additionally, lorcaserin also suppressed GSIS in high-fat diet (HFD)-fed mice in dose-dependent manner. Lorcaserin did not change insulin synthesis ATP content, but lorcaserin decrease cytosolic free calcium level [(Ca2+)i] in MIN6 cells stimulated with glucose and also inhibit insulin secretion and (Ca2+)i in MIN6 treated with potassium chloride. Furthermore, stimulation with the L-type channel agonist, Bay K8644 did not restore GSIS in MIN6 exposed to lorcaserin. Lorcaserin inhibits the cAMP generation of MIN6 cells and pretreatment with the Gα i/o inhibitor pertussis toxin (PTX), abolished lorcaserin-induced suppression of GSIS in β cells, while membrane-permeable cAMP analogue db-cAMP had same effect as PTX. These date indicated lorcaserin coupled to PTX-sensitive Gα i/o proteins in β cells reduced intracellular cAMP level and Ca2+ influx, thereby causing GSIS dysfunction of β cell. These results highlight a novel signaling mechanism of lorcaserin and provide valuable insights into the further investigation of 5-HT2CR functions in β-cell biology and it also provides guidance for the clinical application of lorcaserin.
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Project description:Calcium acts as a universal second messenger to regulate gene expression in both developmental processes and responses to environmental stresses. Previous studies showed that a number of stimuli can induce calcium increases in the cytoplasm and nucleus, independently. However, the gene expression network deciphering [Ca2+]cyt and/or [Ca2+]nuc signaling pathway remain obscure. Using transgenic Arabidopsis containing a fusion protein, comprising rat parvalbumin (PV) with either a nuclear export sequence (PV-NES) or a nuclear localization sequence (NLS-PV), to selectively buffer the cytosolic or nucleosolic calcium, we identified the [Ca2+]cyt- or /and [Ca2+]nuc-regulated ABA- and MeJA-responsible genes with the Arabidopsis Genome Oligo array.
2018-01-25 | GSE109611 | GEO
Project description:Intrauterine growth restriction is a common complication of pregnancy. We induce IUGR in rats by bilateral uterine artery ligation at e18 of a 23 day gestation. This mimics placental insufficiency. This array experiment compares gene expression changes in isolated pancreatic islets from e19, 24 hours post-surgery , or sham operated animals. RNA from isolated pancreatic islets from e19 fetuses, pooled from an entire litter. There are 4 control (sham) operated litters and 4 IUGR litters.
2013-07-10 | E-GEOD-48655 | biostudies-arrayexpress
Project description:Intramuscular fat (IMF) in pork holds significant importance for economic performance within the pig industry and dietary calcium supplementation enhances the accumulation of intramuscular fat. Additionally, calcium ions inhibit translation and reduce protein synthesis. However, the mechanism by which calcium regulates IMF deposition in muscle through translation remains largely unknown. In this study, we compared the ribosome profiles of the longissimus dorsi muscles of trigram pigs from the normal calcium (NC) group or calcium supplement (HC) group by Ribo-seq, and RNA-seq. By integrating multiple-omics analysis, we further discovered 437 genes that were transcriptionally unchanged but translationally altered and these genes
2024-04-22 | GSE264551 | GEO
Project description:We report the application of RNA-seq for molecular profiling of cultured, cortical astrocytes. Our data set is based on about 40 million unique reads per sample in four independent mRNA preparations. Cortical astrocytes are a prototypical cell model for investigating calcium signaling. For analysis of calcium fluxes, we performed direct calcium imaging in the endoplasmic reticulum and in the cytosol. We describe in our study the physiological profile of homeostatic and agonist-induced calcium fluxes. Furthermore, we show how ER calcium release shapes the cytosolic calcium signal. This transcriptome dataset was used to profile the calcium toolkit of astrocytes. The data suggest that a small number of calcium signaling-related proteins mediate calcium homeostasis in astrocytes.
2021-12-14 | GSE166464 | GEO
Project description:Homeostatic calcium fluxes, ER calcium release, SOCE, and calcium oscillations in cultured astrocytes are interlinked by a small calcium toolkit
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Project description:To investigate gene expression differences between human stem cell-derived islets and human islets before transplantation. We performed gene expression profiling analysis using data obtained from RNA-seq of 5 different batches of stem cell-derived islets and human islets from 7 donors.
2024-05-22 | GSE221383 | GEO