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IAPP-induced beta cell toxicity recapitulates islet molecular pathology in type 2 diabetes

ABSTRACT: IAPP-induced beta cell toxicity recapitulates islet molecular pathology in type 2 diabetes

PROVIDER: PRJNA625798 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11558400_1.fastq.gz	Fastqsanger.gz
	SRR11558400_2.fastq.gz	Fastqsanger.gz
	SRR11558386_1.fastq.gz	Fastqsanger.gz
	SRR11558386_2.fastq.gz	Fastqsanger.gz
	SRR11558387_1.fastq.gz	Fastqsanger.gz

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IAPP-induced beta cell toxicity recapitulates islet molecular pathology in type 2 diabetes

Project description:Islets in Type 2 diabetes (T2D) share many diverse abnormalities reported in neurodegenerative diseases, including the formation of toxic oligomers from amyloidogenic proteins. We evaluated the transcriptome of murine islets with beta cell-specific human IAPP (hIAPP) expression to assess the potential contribution of hIAPP toxicity to those observed in islets from T2D.Beta cell hIAPPtoxicity induced an islet transcriptome highly analogous to that in islets from humans with T2D with a prominent inflammatory signature, activation of vascular epithelium and stellate cells, cytoskeleton remodeling,and activation of cell-cycle andcellular dedifferentiation. In conclusion, many of the apparently widely disparate changes in islets in T2D may be initiated by toxic oligomers. Inhibition of expression of amyloidogenic proteins or proximal adverse consequences such as disruption of the cytoskeleton by calpain hyperactivation are rational targets for therapeutic intervention in T2D and neurodegenerative disease.

2021-10-21 | GSE148809 | GEO

Repositioning the early pathology of type 1 diabetes to the extra-islet vasculature.

Project description:Repositioning the early pathology of type 1 diabetes to the extra-islet vasculature.

2024-02-01 | GSE253956 | GEO

transcriptional profile of islet EVs for diabetes genes

Project description:Identification of transcriptional profile of several genes involved in diabetes in islet-derived extracellular vesicles (Evs). Recently, EVs are identified as a new mechanism in cell-to-cell communication by transfer of protein and genic information (mRNA, microRNA). Their role is under investigation in immunology, stem cell and cancer, but not in islets and diabetes. The aim of this experiment is to identify mRNA transcripts (in particular, mRNA transcripts involved in diabetes pathophysiology) present in islet Evs.

2012-08-02 | E-MEXP-3695 | biostudies-arrayexpress

Islet Sympathetic Innervation and Islet Neuropathology in Patients with Type 1 Diabetes

Project description:Dysregulation of glucagon secretion in type 1 diabetes (T1D) involves hypersecretion during postprandial states, but insufficient secretion during hypoglycemia. The sympathetic nervous system regulates glucagon secretion. To investigate islet sympathetic innervation in T1D, sympathetic tyrosine hydroxylase (TH) axons were analyzed in control non-diabetic organ donors, non-diabetic islet autoantibody-positive individuals (AAb), and age-matched persons with T1D. Islet TH axon numbers and density were significantly decreased in AAb compared to T1D with no significant differences observed in exocrine TH axon volume or lengths between groups. TH axons were in close approximation to islet α-cells in T1D individuals with long-standing diabetes. Islet RNA-sequencing and qRT-PCR analyses identified significant alterations in noradrenalin degradation, α-adrenergic signaling, cardiac b-adrenergic signaling, catecholamine biosynthesis, and additional neuropathology pathways. The close approximation of TH axons at islet α-cells supports a model for sympathetic efferent neurons directly regulating glucagon secretion. Sympathetic islet innervation and intrinsic adrenergic signaling pathways could be novel targets for improving glucagon secretion in T1D.

2021-08-09 | GSE181674 | GEO

Neuronal VCP loss of function recapitulates FTLD-TDP pathology

Project description:Neuronal VCP loss of function recapitulates FTLD-TDP pathology

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Transcriptional changes underlying progression from islet autoantibody positivity to type 1 diabetes

Project description:Type 1 diabetes (T1D) usually has a preclinical phase identified by the presence of circulating autoantibodies to pancreatic islet antigens, and most young children who have multiple autoantibodies progress to diabetes within 10 years. While autoantibodies denote underlying islet autoimmunity, how this process is initiated and then progresses to clinical diabetes on a background of genetic susceptibility is not clearly understood. We analysed gene expression by RNA-seq in four types of immune cells from five genetically at-risk children with islet autoantibodies who progressed to diabetes in ≤ 3 years (‘progressors’) and in five at-risk children matched for sex, age and HLA who had not progressed to diabetes (‘non-progressors’).

2022-03-09 | GSE185190 | GEO

Whole population RNASeq of pancreatic islet macrophages during autoimmune diabetes progression

Project description:Whole population RNASeq of pancreatic islet macrophages during autoimmune diabetes progression.

2020-03-27 | GSE141782 | GEO

Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes

Project description:<h4><strong>AIMS/HYPOTHESIS: </strong>Metabolic dysregulation may precede the onset of type 1 diabetes. However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. In this study, we examined whether children who progress to type 1 diabetes have a circulatory polar metabolite profile distinct from that of children who later progress to islet autoimmunity but not type 1 diabetes and a matched control group.</h4><h4><strong>METHODS: </strong>We analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to type 1 diabetes; those who seroconverted to one islet autoantibody but not to type 1 diabetes; and an antibody-negative control group. Metabolites were measured using two-dimensional GC high-speed time of flight MS.</h4><h4><strong>RESULTS: </strong>In early infancy, progression to type 1 diabetes was associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, compared with the control group. Methionine remained persistently upregulated in those progressing to type 1 diabetes compared with the control group and those who seroconverted to one islet autoantibody. The appearance of islet autoantibodies was associated with decreased glutamic and aspartic acids.</h4><h4><strong>CONCLUSIONS/INTERPRETATION: </strong>Our findings suggest that children who progress to type 1 diabetes have a unique metabolic profile, which is, however, altered with the appearance of islet autoantibodies. Our findings may assist with early prediction of the disease.</h4>

2022-01-19 | MTBLS802 | MetaboLights

Proteomic pathways to metabolic disease and type 2 diabetes in the pancreatic islet

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

Islet Sympathetic Innervation and Islet Neuropathology in Patients with Type 1 Diabetes

Project description:Islet Sympathetic Innervation and Islet Neuropathology in Patients with Type 1 Diabetes

| PRJNA752997 | ENA