Pancreatic islets communicate with lymphoid tissues via exocytosis of insulin peptides
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA472771 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: Not available
| S-EPMC6090537 | biostudies-literature
Project description:Blattella germanica Insulin-like Peptides (ILPs)
| PRJEB23932 | ENA
Project description:A difference in the transcriptomes of 8F10 T cells sourced from the NOD (8F10-NOD) or B16A (8F10-B16A) hosts was analyzed. As a result we found a number of biological pathways upregulated in the 8F10-NOD T cells including oxidative phosphorylation (OXPHOS), Myc targets, fatty acid metabolism, mTOR complex 1 (mTORC1) signaling.
2018-07-18 | GSE114824 | GEO
Project description:Pancreatic islets are central in type 2-diabetes development, which coincides with increased activity of innate immunity. Intriguingly, human pancreatic islets express many complement genes. The most highly expressed gene was the complement inhibitor CD59 that is GPI anchored to the cell membrane, which unexpectedly was found in high amounts intracellularly in beta cells. Silencing of CD59 strongly suppressed insulin secretion. Importantly, this suppression was unrelated to established CD59 functions, but rather depletion of intracellular CD59. Imaging experiments identified a distal site of inhibition in the exocytotic pathway, but prior to emptying of the insulin granules. Proximity Ligation Assays pin-pointed the mechanism to impaired turnover of exocytosis-regulating SNARE-proteins and CD59 was detected in complex with VAMP2 and syntaxin. CD59 was downregulated by 24-h glucose incubations in human islets, rat cell lines and in islets from three rodent diabetes models. Islets from cadaver donors were provided by the Nordic Islet Transplantation Programme (www.nordicislets.org), Uppsala University. The microarrays were performed using GeneChipM-BM-. Human Gene 1.0 ST whole transcript according to Affymetrix standard protocol.
2014-03-02 | E-GEOD-54279 | biostudies-arrayexpress
Project description:The study was completed to compare expression profiles of primary human beta cells (in the form of adult human islets), to the expression profile of hESC-derived beta-like cells. A HES3 line modified by homologous recombination to express GFP under the insulin promoter allowed us to FACS sort the hESC-derived cells into purified insulin-positive (presumably beta-like cells), and insulin-negative populations. Expression profile of adult human islets from cadaveric donors is compared to insulin-positive and insulin-negative populations of hESC-derived beta-like cells
2012-09-09 | E-GEOD-40709 | biostudies-arrayexpress
Project description:Pancreatic islets are central in type 2-diabetes development, which coincides with increased activity of innate immunity. Intriguingly, human pancreatic islets express many complement genes. The most highly expressed gene was the complement inhibitor CD59 that is GPI anchored to the cell membrane, which unexpectedly was found in high amounts intracellularly in beta cells. Silencing of CD59 strongly suppressed insulin secretion. Importantly, this suppression was unrelated to established CD59 functions, but rather depletion of intracellular CD59. Imaging experiments identified a distal site of inhibition in the exocytotic pathway, but prior to emptying of the insulin granules. Proximity Ligation Assays pin-pointed the mechanism to impaired turnover of exocytosis-regulating SNARE-proteins and CD59 was detected in complex with VAMP2 and syntaxin. CD59 was downregulated by 24-h glucose incubations in human islets, rat cell lines and in islets from three rodent diabetes models.
2014-03-02 | GSE54279 | GEO
Project description:The nature of autoantigens that trigger autoimmune diseases has been much discussed but direct biochemical identification is lacking for most. Addressing this question demands unbiased examination of the self-peptides displayed by a defined autoimmune MHC-II molecule. We have examined the immunopeptidome of the pancreatic islets of the NOD mouse that spontaneously develops autoimmune diabetes based on its MHC-II, the I-Ag7 variant. The relevant peptides that induced early CD4 T cells derived from insulin and C-peptide; these were also found in the MHC-II peptidome of the pancreatic lymph node and spleen. The insulin-derived peptides followed a trajectory from internal processing in beta cells to exocytosis, uptake, and presentation in islets and peripheral sites. Such process not only generated conventional epitopes but also resulted in presentation of post-translationally modified peptides, including deamidated and fused sequences. These analyses reveal the key features of a restricted component in the self-MHC-II peptidome causing autoreactivity.
2020-03-12 | PXD015408 | Pride
Project description:Expression studies in several models of type 2 Diabetes have suggested that exocytosis contributes to the modulation of insulin secretion during the 24h cycle. In agreement with the activity and feeding pattern of nocturnal rodents, we find that C57/Bl6J mice exhibit higher insulin secretion during the dark phase (ZT20 vs ZT8). Glucose-induced insulin secretion is increased by 21% despite normal intracellular Ca2+ signaling and depolarization-evoked exocytosis as measured by whole-cell capacitance measurements. This paradox is explained by a 1.37-fold increase in beta cell insulin content. Ultramorphological analysis show that vesicle size and density are unaltered but the intravesicular content per granule is modulated during the circadian rhythm. Proinsulin levels were not statistically different between the two time points despite a trend for reduction at ZT20. Islet glucagon content was inversely proportional to insulin content. Microarray data identified the differential expression of 301 transcripts of which, 54 known genes and 26 miRNA, including clock genes such as Bmal1 and Rev-erb . Differential expression of C2cd4b may contribute to the modulation of insulin content. Mice -cell secretion during the 24h cycle may rely on several distinct cellular functions but late night increase in insulin secretion depends solely on granule insulin content. A total of 301 genes were differentially expressed between ZT8 vs ZT20 islets . A majority were upregulated (199 between 1.3 to 2.71 fold) whilst 102 were down-regulated (<-1.3 fold). Given the focus of our study, current literature and our own results, genes involved in exocytosis, insulin production and of course, circadian rhythms were particularly interesting.
2018-01-31 | GSE109882 | GEO
Project description:Hyperinsulinemia often precedes type 2 diabetes but its role in disease progression is unknown. Palmitoylation, a protein modification implicated in regulated exocytosis, is reversed by acyl-protein thioesterase 1 (APT1). We found altered APT1 biology in pancreatic islets from humans with type 2 diabetes, and APT1 knockdown in nondiabetic human islets caused insulin hypersecretion. Chow fed global and islet specific APT1 knockout mice had enhanced glucose tolerance due to islet autonomous increased glucose-stimulated insulin secretion. APT1 deficiency did not affect islet calcium dynamics but prolonged insulin granule fusion. Using palmitoylation proteomics, we identified Scamp1 as an APT1 substrate that localized to insulin secretory granules. Knockdown of Scamp1 caused insulin hypersecretion. APT1 deficient insulinoma cells subjected to nutrient excess had increased apoptosis, and expression of a mutated Scamp1 incapable of being palmitoylated in APT1 deficient cells rescued insulin hypersecretion and nutrient induced apoptosis. Compared to APT1 sufficient controls, high fat fed islet specific APT1 knockout mice and global APT1 deficient db/db mice showed increased -cell failure. These findings suggest that the depalmitoylation enzyme APT1 is regulated in human islets, and that APT1 deficiency causes insulin hypersecretion leading to -cell failure, modeling the evolution of some forms of human type 2 diabetes.
2023-11-05 | PXD038554 | Pride
Project description:Tafazzin is a transacylase which causes the content and molecular structure of cardiolipin (CL) to be altered in the inner mitochondrial membrane. The enzymatic machinery responsible for oxidative respiration are localized to the inner mitochondrial membrane and require CL for activity. As a result, tafazzin is critical for maintaining mitochondrial function. In beta-cells, which are the insulin secreting cells in pancreatic islets, mitochondrial function is linked to insulin secretion. We previously established that tafazzin knock-down mice were lean and maintained insulin sensitivity compared to the obese insulin resistant control litter mates. However, it was unknown whether tafazzin deficiency also influenced insulin secretion in the establishment of the lean phenotype. Using X week-old mice, we ascertained that the number of beta-cells was similar between genotypes. Ex vivo insulin secretion under low glucose conditions was reduced (52%) from islets isolated from tafazzin knock-down mice. Consistent with this tafazzin knock-down mice exhibited reduced fasting insulin plasma insulin levels. Measurement of mitochondrial oxygen consumption revealed that basal oxygen consumption was reduced (58%) in islets from tafazzin-deficient animals. The addition of etomoxir, an inhibitor of mitochondrial fatty acid translocation, significantly elevated basal mitochondrial respiration (5-fold) in islets from tafazzin knockdown mice, indicating a significant fatty acid-mediated inhibitory effect. In contrast, etomoxir lacked any measurable effect on control wild-type islets. The altered mitochondrial function identified in taffazin knock-down islets was not associated with reduced CL content or elevated oxyCL species. Our experiments indicate that tafazzin plays a key role in regulating normal islet beta-cell function.
2021-07-31 | GSE136242 | GEO