Insulinoma‐released exosomes activate autoreactive marginal zone‐like <scp>B</scp> cells that expand endogenously in prediabetic <scp>NOD</scp> mice

Bashratyan, Roman; Sheng, Huiming; Regn, Danielle; Rahman, M. Jubayer; Dai, Yang

doi:10.1002/eji.201343376

Cited by 55 publications

(48 citation statements)

References 47 publications

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“…Taking advantage of MIN6 ELVs’ ability to steer immune responses72830, we used murine RAW264.7 macrophages to assess for biological activity. When treated with 20 μg/ml of fresh fluorescently labelled beta-ELVs for six hours and analysed by flow cytometry, beta-ELV uptake led to an increase in CFDA-SE positive RAW264.7 cells in 43.0% of beta-ELV treated cells at 37 °C (Fig.…”

Section: Resultsmentioning

confidence: 99%

Trehalose prevents aggregation of exosomes and cryodamage

Bosch¹,

Beaurepaire²,

Allard³

et al. 2016

Sci Rep

263

206

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Exosomes are important mediators in intercellular communication. Released by many cell types, they transport proteins, lipids, and nucleic acids to distant recipient cells and contribute to important physiopathological processes. Standard current exosome isolation methods based on differential centrifugation protocols tend to induce aggregation of particles in highly concentrated suspensions and freezing of exosomes can induce damage and inconsistent biological activity. Trehalose is a natural, non-toxic sugar widely used as a protein stabilizer and cryoprotectant by the food and drug industry. Here we report that addition of 25 mM trehalose to pancreatic beta-cell exosome-like vesicle isolation and storage buffer narrows the particle size distribution and increases the number of individual particles per microgram of protein. Repeated freeze-thaw cycles induce an increase in particle concentration and in the width of the size distribution for exosome-like vesicles stored in PBS, but not in PBS 25 mM trehalose. No signs of lysis or incomplete vesicles were observed by cryo-electron tomography in PBS and trehalose samples. In macrophage immune assays, beta-cell extracellular vesicles in trehalose show consistently higher TNF-alpha cytokine secretion stimulation indexes suggesting improved preservation of biological activity. The addition of trehalose might be an attractive means to standardize experiments in the field of exosome research and downstream applications.

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Section: Resultsmentioning

confidence: 99%

Trehalose prevents aggregation of exosomes and cryodamage

Bosch¹,

Beaurepaire²,

Allard³

et al. 2016

Sci Rep

263

206

View full text Add to dashboard Cite

show abstract

“…Increased cytokine levels then induce endoplasmic reticulum stress in β‐cells, resulting in increased exosome secretion and the establishment of a vicious circle . Exosomes released by the insulinoma line MIN6 contain candidate autoantigens that result in T cell proliferation and B cell activation . Similarly, CD105 + mesenchymal stem cells present in pancreatic islets of nonobese diabetic (NOD) mice release exosomes with immunomodulatory capabilities that accelerate T cell‐mediated destruction of the islets .…”

Section: Exosomes and Evs In Diabetesmentioning

confidence: 99%

Exosomes and diabetes

Castaño

Novials

Párrizas

2019

Diabetes Metabolism Res

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Summary Diabetes is a group of metabolic diseases characterized by elevated blood glucose levels that drive the development of life‐threatening complications. Diabetes results from a situation of insufficient insulin action, either by deficient production of the hormone by the pancreas, or by the development of insulin resistance in peripheral tissues such as liver, muscle, or the adipose depots. Communication between organs is thus central to the maintenance of glucose homoeostasis. Recently, several studies are evidencing that small vesicles called exosomes released by, amongst other, the adipose tissue can regulate gene expression in other tissues, hence modulating interorgan crosstalk. Therefore, exosomes participate in the development of diabetes and its associated complications. Their study holds the potential of providing us with novel biomarkers for the early diagnosis and stratification of patients at risk of developing diabetes, hence allowing the timely implementation of more personalized therapies. On the other hand, the molecular dissection of the pathways initiated by exosomes under situations of metabolic stress could help to gain a deeper knowledge of the pathophysiology of diabetes and its associated metabolic diseases.

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“…In recent years, several specific miRNAs have also been shown to play important roles in both the regulation of β cell function and the pathogenesis of Type 1 diabetes (22). Although, miRNAs are intracellular origin, they may also be secreted extracellularly, either through microvesicles or exosomes, which can then be taken up by different cells to influence their gene expression patterns (23–25). Compared to mRNA species, miRNAs are invariably more stable in biological fluids, where they have been detected in high abundance in blood, urine, saliva, cerebrospinal fluid, milk, seminal fluid, and amniotic fluid (26).…”

Section: Differentially Expressed Mirnas In Type 1 Diabetesmentioning

confidence: 99%

Nucleic acid biomarkers of β cell stress and death in type 1 diabetes

Syed

Evans‐Molina²

2016

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of the review The purpose of this review is to summarize recent advances in the development of nucleic acid-based biomarkers in type 1 diabetes (T1D). Recent findings Recent rodent and human studies have identified new roles for stress pathways intrinsic to the β cell during the development of T1D. As such, methods to identify an authentic nucleic acid signature of β cell stress and/or death may improve our ability to predict T1D at earlier timepoints, allowing for optimal timing of immunomodulatory interventions. To this end, both targeted and unbiased approaches have begun to identify changes in microRNA expression patterns in T1D. Moreover, a number of groups have developed distinct assays that quantitatively detect circulating unmethylated insulin DNA, which is thought to primarily emanate from dying β cells. Summary Here we highlight unique blood and urine miRNA signatures identified in T1D cohorts, compare differences between first, second, and third generation assays that detect circulating unmethylated insulin DNA, and review recent technological advances that have the capacity to improve T1D biomarker development.

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Insulinoma‐released exosomes activate autoreactive marginal zone‐like B cells that expand endogenously in prediabetic NOD mice

Cited by 55 publications

References 47 publications

Trehalose prevents aggregation of exosomes and cryodamage

Trehalose prevents aggregation of exosomes and cryodamage

Exosomes and diabetes

Nucleic acid biomarkers of β cell stress and death in type 1 diabetes

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