Ghrelin deletion and conditional ghrelin-cell ablation increase pancreatic islet size in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE244390 | GEO | 2023/11/06
REPOSITORIES: GEO
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Project description:Ghrelin deletion and conditional ghrelin-cell ablation increase pancreatic islet size in mice
| PRJNA1022509 | ENA
Project description:Ghrelin exerts key effects on islet hormone secretion to regulate blood glucose levels. Here, we sought to determine whether ghrelin's effects on islets extend to the alteration of islet size and β cell mass. We demonstrate that reducing ghrelin - by ghrelin gene knockout (GKO), conditional ghrelin cell ablation, or high-fat diet (HFD) feeding - was associated with increased mean islet size (up to 62%), percentage of large islets (up to 854%), and β cell cross-sectional area (up to 51%). In GKO mice, these effects were more apparent in 10- to 12-week-old mice than in 4-week-old mice. Higher β cell numbers from decreased β cell apoptosis drove the increase in β cell cross-sectional area. Conditional ghrelin cell ablation in adult mice increased the β cell number per islet by 40% within 4 weeks. A negative correlation between islet size and plasma ghrelin in HFD-fed plus chow-fed WT mice, together with even larger islet sizes in HFD-fed GKO mice than in HFD-fed WT mice, suggests that reduced ghrelin was not solely responsible for diet-induced obesity-associated islet enlargement. Single-cell transcriptomics revealed changes in gene expression in several GKO islet cell types, including upregulation of Manf, Dnajc3, and Gnas expression in β cells, which supports decreased β cell apoptosis and/or increased β cell proliferation. These effects of ghrelin reduction on islet morphology might prove useful when designing new therapies for diabetes.
| S-EPMC10721155 | biostudies-literature
Project description:Intra-islet crosstalk between islet cells is critical in orchestrating the body’s response to changes in blood glucose levels, but is incompletely understood. In this study, we used transgenic mouse lines that allowed the purification and transcriptomic characterisation of alpha, beta, and delta cells, yielding an RNA-sequencing database that can be searched for regulatory proteins which are differentially expressed between cell types. As an illustrative example, we examined the expression of g-protein coupled receptors, and found that the ghrelin receptor, Ghsr, was highly expressed in delta cells compared to alpha and beta cells. GHSR excitation elicited increases in cytosolic calcium levels in primary delta cells. In the perfused pancreas, the application of ghrelin stimulated somatostatin secretion, correlating with a decrease in insulin and glucagon release, which was sensitive to somatostatin receptor antagonism. These results show that ghrelin acts specifically on delta cells within pancreatic islets to affect blood glucose regulation.
2016-07-11 | GSE76017 | GEO
Project description:LCM-coupled nanoPOTS proteomics using FAIMS of intra-islet microstructures. 5 acinar samples, 5 whole islets, 5 islet interface vasculature pools, 5 islet inner microvasculature pools, 3 islets after microsvasculature removed.
2022-01-25 | MSV000088730 | MassIVE
Project description:We measured changes in the human islet proteome following 72-hr exposure to 3 mM R-beta-hydroxybutyrate. Islets from 12 metabolically healthy human islet donors were obtained from the Alberta Diabetes Institute Islet Core
2024-06-17 | MSV000095058 | MassIVE
Project description:Using intravital 2-photon islet imaging we show that T cell extravasation into the islets is an extended process, with T cells arresting in the islet vasculature in close proximity to perivascular CD11c+ cells. Antigen is not required for T cell trafficking to infiltrated islets, but T cell chemokine receptor signaling is necessary. Using RNAseq, we show that islet CD11c+ cells express over 20 different chemokines that bind chemokine receptors expressed on islet T cells.
2019-03-01 | GSE121804 | GEO
Project description:Pancreatic islets are essential for maintaining physiological blood glucose levels, and declining islet function is a hallmark of type 2 diabetes. Here we employ mass spectrometry (MS)-based proteomics to systematically analyse purified islets from 9 genetic or diet-induced mouse models representing a broad cross-section of metabolic health. Quantifying the islet proteome to a depth of >11,500 proteins, this study represents the most detailed analysis of islet proteins to date. Our data highlight that the vast majority of islet proteins are expressed in all strains and diets, but more than half of the proteins vary in expression levels. Associating these varied protein expression levels on an individual animal basis with individual phenotypic measures reveals islet mitochondrial function as a major positive indicator of metabolic health. This compendium of strain-specific and dietary changes to mouse islet proteomes represents a comprehensive resource for basic and translational islet cell biology.
2021-10-08 | PXD024522 | Pride
Project description:Hepatic fibrosis, the wound-healing response to repeated liver injury, ultimately leads to cirrhosis. There is an urgent need to develop effective antifibrotic therapies. Ghrelin (encoded by Ghrl) is an orexigenic hormone that has pleiotrophic functions including protection against cell death1. Here we investigate whether ghrelin modulates liver fibrosis and protects from acute liver injury. Recombinant ghrelin reduced the fibrogenic response to prolonged bile duct ligation in rats. This effect was associated with decreased liver injury and myofibroblast accumulation as well as attenuation of the altered gene expression profile. Ghrelin also reduced fibrogenic properties in cultured hepatic stellate cells. Moreover, Ghrl-/- mice developed exacerbated hepatic fibrosis and liver damage after chronic injury. Ghrelin also protected rat livers from acute liver injury and reduced the extent of oxidative stress and the inflammatory response. In patients with chronic liver diseases, ghrelin serum levels decreased in those with advanced fibrosis and hepatic expression of the ghrelin gene correlated with expression of fibrogenic genes. Finally, in patients with chronic hepatitis C, single nucleotide polymorphisms of the ghrelin gene (-994CT and â604GA) influenced the progression of liver fibrosis. We conclude that ghrelin exerts antifibrotic effects on the liver and may represent a novel antifibrotic therapy. Experiment Overall Design: Rats were divided into three groups: control rats receiving saline (sham operation), rats with bile duct ligation receiving saline and rats with bile duct ligation receiving recombinant ghrelin (10 micrograms/Kg/day by a subcutaneous osmotic mimi-pump). For the microarray analysis samples from 6 rats were analyzed except for the ghrelin-treated group (5 rats).
2009-01-13 | E-GEOD-13747 | biostudies-arrayexpress
Project description:We anticipated that the identification of cis-regulatory regions active in pancreatic islets would help increase our understanding of islet biology and the pathology of diabetes. Towards this end we used histone H3 lysine 4 monomethylation-based nucleosome predictions genome-wide, in conjunction with binding data for PDX1, FOXA2, MAFA, and NEUROD1, to identify 3,654 putative enhancers that are H3K4me1-enriched uniquely in islets as compared to 14 other tissue or cell-types. We show that these islet-specific enhancers are associated with genes with significantly higher islet specificity than genes associated with non-specific enhancers. Further, islet-specific enhancers were not enriched for typical active or repressive histone methylations in embryonic stem cells and liver, suggesting they are formed by de novo histone methylation during pancreas development. We also identify a subset of enhancers bivalently marked by both H3K4me1 and H3K27me3 in adult pancreatic islets. Further, we show that islet-specific enhancers triple- or quadruple- bound by PDX1, MAFA, NEUROD1 and/or FOXA2 are associated with genes with particularly high islet-specificity, and that these loci are enriched in regions with functional activity in islet cell types. Finally, we demonstrate that cytokines reduce H3K4me1 enrichment levels at selected triple- or quadruple-bound islet-specific enhancers, suggesting that epigenetic changes may contribute to cytokine-induced b-cell dysfunction. In conjunction with data from Hoffman et al Genome Research 2010, an analysis of histone modifications and transcription factor binding sites to identify enhancer regions
2011-06-30 | E-GEOD-30298 | biostudies-arrayexpress
Project description:Transgenic mice were generated that expressed the inhibitor of apoptosis and mitotic regulator survivin in pancreatic islet beta cells. Control non-transgenic or transgenic islets were then used in a model of islet transplantation in diabetic recipient mice and tested for their ability to correct hyperglycemia and allow long-term engraftment of tranplanted islets in vivo. Control or transgenic islets were analyzed by chip microarray for potential transcriptional changes associated with transgenic expression of survivin, in vivo.
2006-01-16 | E-MEXP-536 | biostudies-arrayexpress