Extracellular vesicles from human pancreatic islets suppress human islet amyloid polypeptide amyloid formation

Ribeiro, Diana; Horváth, István; Heath, Nikki; Hicks, Ryan; Forslöw, Anna; Wittung-Stafshede, Pernilla

doi:10.1073/pnas.1711389114

Cited by 34 publications

(36 citation statements)

References 48 publications

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“…PS on these extracellular vesicles interacts with receptors for PS on the surface of various cells including phagocytes, endothelial cells, dendritic cells, and epithelial cells, thereby inducing cellular uptake of the extracellular vesicles 72 , 73 . Importantly, extracellular vesicles such as exosomes reportedly affect the formation of amyloid fibrils by some amyloidogenic proteins such as α-synuclein 74 and IAPP 75 . These lines of evidence together with our findings suggest that extracellular vesicles secreted from a certain type of cells can contribute to or regulate the pathology of amyloidoses.…”

Section: Discussionmentioning

confidence: 99%

Effect of Phosphatidylserine and Cholesterol on Membrane-mediated Fibril Formation by the N-terminal Amyloidogenic Fragment of Apolipoprotein A-I

Mizuguchi

Nakamura

Kurimitsu

et al. 2018

Sci Rep

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Here, we examined the effects of phosphatidylserine (PS) and cholesterol on the fibril-forming properties of the N-terminal 1‒83 fragment of an amyloidogenic G26R variant of apoA-I bound to small unilamellar vesicles. A thioflavin T fluorescence assay together with microscopic observations showed that PS significantly retards the nucleation step in fibril formation by apoA-I 1‒83/G26R, whereas cholesterol slightly enhances fibril formation. Circular dichroism analyses demonstrated that PS facilitates a structural transition from random coil to α-helix in apoA-I 1‒83/G26R with great stabilization of the α-helical structure upon lipid binding. Isothermal titration calorimetry measurements revealed that PS induces a marked increase in capacity for binding of apoA-I 1‒83/G26R to the membrane surface, perhaps due to electrostatic interactions of positively charged amino acids in apoA-I with PS. Such effects of PS to enhance lipid interactions and inhibit fibril formation of apoA-I were also observed for the amyloidogenic region-containing apoA-I 8‒33/G26R peptide. Fluorescence measurements using environment-sensitive probes indicated that PS induces a more solvent-exposed, membrane-bound conformation in the amyloidogenic region of apoA-I without affecting membrane fluidity. Since cell membranes have highly heterogeneous lipid compositions, our findings may provide a molecular basis for the preferential deposition of apoA-I amyloid fibrils in tissues and organs.

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Section: Discussionmentioning

confidence: 99%

Effect of Phosphatidylserine and Cholesterol on Membrane-mediated Fibril Formation by the N-terminal Amyloidogenic Fragment of Apolipoprotein A-I

Mizuguchi

Nakamura

Kurimitsu

et al. 2018

Sci Rep

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show abstract

“…In steady-state conditions it regulates food intake, insulin secretion, and glucose metabolism ( 94 ). Ribeiro et al have noted that pancreatic extracellular vesicles (EVs) from healthy individuals, but not from T2DM patients, directly bind to IAPPs and prevent amyloid formation within the pancreatic islets ( 95 ). The authors showed that the altered protein-lipid composition of the EVs is the main reason for this discrepancy ( 95 ).…”

Section: Effects Of T2dm On the Digestive Systemmentioning

confidence: 99%

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

et al. 2020

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Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro-and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.

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“…A group investigating treatments for diabetes focused on pancreatic amyloid deposits in T2D, which have been shown to be a contributor to the disease. Researchers found that secreted exosomes from healthy, but not from T2D patients could slow amyloid formation in in vitro models of T2D . The therapeutic potential of MSC‐derived exosomes was investigated in animal models of diabetes.…”

Section: Role Of Exosomesmentioning

confidence: 99%

Exosomes in Inflammation and Inflammatory Disease

et al. 2019

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Exosomes are a subset of extracellular vesicles released by all cell types and involved in local and systemic intercellular communication. In the past decade, research into exosomes has swelled as their important role in the mediation of health and disease has been increasingly established and acknowledged. Exosomes carry a diverse range of cargo including proteins, nucleic acids, and lipids derived from their parental cell that, when delivered to the recipient cell, can confer pathogenic or therapeutic effects through modulation of immunity and inflammation. In this review, the role of exosomes on mediation of immune and inflammatory responses, and their participation in diseases with a significant inflammatory component is discussed. The considerable potential for exosomes in therapy and diagnosis of inflammatory diseases is also highlighted.

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Extracellular vesicles from human pancreatic islets suppress human islet amyloid polypeptide amyloid formation

Cited by 34 publications

References 48 publications

Effect of Phosphatidylserine and Cholesterol on Membrane-mediated Fibril Formation by the N-terminal Amyloidogenic Fragment of Apolipoprotein A-I

Effect of Phosphatidylserine and Cholesterol on Membrane-mediated Fibril Formation by the N-terminal Amyloidogenic Fragment of Apolipoprotein A-I

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

Exosomes in Inflammation and Inflammatory Disease

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