Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: Controversial points and a promising arena

Journal of Diabetes, Год журнала: 2023, Номер 15(5), С. 397 - 408

Опубликована: Апрель 19, 2023

Abstract Neprilysin (NEP) is a transmembrane zinc‐dependent metalloproteinase that inactivates various peptide hormones including glucagon‐like 1 (GLP‐1). NEP inhibitors may be effective in the management of type 2 diabetes mellitus (T2DM) by increasing circulating level GLP‐1. However, acute‐effect lead to detrimental effects blood glucose independent These findings suggest controversial point regarding potential role on homeostasis T2DM patients. Therefore, this perspective aimed clarify points concerning T2DM. beneficial inhibition NEP, which involved impairment through modulation insulin resistance. increases dipeptidyl peptidase‐4 (DPP4) activity and contributes active GLP‐1 proteolysis so improve glycemic control endogenous reduction DPP4 activity. Thus, could alone or combination with antidiabetic agents treating long‐term short‐term effect sensitivity different mechanisms augmentation substrates pancreatic amyloid deposition. are confirmed animal but not humans. In conclusion, produce rather than humans though most studies.

Язык: Английский

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Efficient optical plasmonic tweezer-controlled single-molecule SERS characterization of pH-dependent amylin species in aqueous milieus

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 2, 2023

It is challenging to characterize single or a few biomolecules in physiological milieus without excluding the influences of surrounding environment. Here we utilize optical plasmonic trapping construct dynamic nanocavity, which reduces diffraction-limited detection volume and provides reproducible electromagnetic field enhancements achieve high-throughput single-molecule surface-enhanced Raman spectroscopy (SERS) characterizations aqueous environments. Specifically, study human Islet Amyloid Polypeptide (amylin, hIAPP) under different pH conditions by combining spectroscopic experiments molecular dynamics (MD) simulations. Based on statistically significant amount time-dependent SERS spectra, two types low-populated transient species hIAPP containing either turn β-sheet structure among its predominant helix-coil monomers are characterized during early-stage incubation at neutral condition, play crucial role driving irreversible amyloid fibril developments even after subsequent adjustment continue prolonged acidic condition. Our results might provide profound mechanistic insight into pH-regulated amyloidogenesis introduce an alternative approach for investigating complex biological processes level.

Язык: Английский

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Antioxidant Polymers with Enhanced Neuroprotection Against Insulin Fibrillation

Macromolecular Bioscience, Год журнала: 2023, Номер 23(7)

Опубликована: Апрель 24, 2023

Lipoic acid (LA) and dihydrolipoic (DHLA) are well established antioxidants to scavenge reactive oxygen species (ROS). However, they carboxylates with ≈4.7 pKa making them negatively charged at physiological pH (7.4) reducing their passive diffusion through cell membranes. LA is known be capable of protein fibrillation. Incorporation especially DHLA in polymer side chains scarce. Herein, the first examples anti-amyloidogenic effect incorporated into side-chain a block copolymer water-soluble poly(polyethylene glycol methyl ether methacrylate) (PPEGMA) segment presented. The resultant polymers show improved ROS scavenging activity ability reduce insulin fibrillation compared free DHLA. Furthermore, also disintegrating preformed firbrils. Interestingly, dihydro-lipoate moieties showed 93% radical 91% anti-fibrillating efficacies for confirmed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay Thioflavin T (ThT) dye binding study, respectively. Further, antioxidant increase viability against fibrillar aggregates that may involved etiology several diseases. Overall, this work reveals polymer-based therapeutic agents can serve as powerful modulation strategy developing novel drugs future amyloid-related disorders.

Язык: Английский

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Essential contributions of food hydrocolloids and phospholipid liposomes to the formation of carriers for controlled delivery of biologically active substances via the gastrointestinal tract

Food Hydrocolloids, Год журнала: 2021, Номер 120, С. 106890 - 106890

Опубликована: Май 10, 2021

Язык: Английский

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Investigation of the effects of two major secretory granules components, insulin and zinc, on human-IAPP amyloid aggregation and membrane damage

Chemistry and Physics of Lipids, Год журнала: 2021, Номер 237, С. 105083 - 105083

Опубликована: Апрель 19, 2021

Язык: Английский

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