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1. The Glucose Effect on Direct Electrochemistry and Electron Transfer Reaction of Glucose Oxidase Entrapped in a Carbon Nanotube‐Polymer Matrix

   https://doi.org/10.1002/slct.202003536  

   Yin, Ziyu; Ji, Zuowei; Zhang, Wendi; Taylor, E_Will; Zeng, Xinping; Wei, Jianjun (October 2020, ChemistrySelect)

   Abstract In this work, glucose oxidase (GOx) cross‐linking to a single‐wall carbon nanotubes (SWCNTs)‐poly(ethylenimine) (PEI) matrix is investigated using cyclic voltammetry (CV) for its direct electrochemistry and kinetics with presence of glucose. The electrochemistry of the bound flavin cofactor, flavin adenine dinucleotide (FAD) of the GOx, is impeded by glucose and recovered at absence of glucose, whereas a non‐specific sugar (e. g. sucrose) has no such effect. The Faradaic current of the GOx in CV decreases when the concentration of glucose increases, while the calculated electron transfer (ET) rate constant (k⁰) of the GOx presents a monotonic increment manner up to 144 % at 70 mM glucose concentration vs. absence of glucose in a deaerated electrolyte solution. Thek⁰and Faradaic current changes demonstrate a strong linear relationship to logarithmic value of glucose concentration up to 20 mM. These results suggest that the entrapped GOx, when exposing to glucose, becomes deactivated in the direct electrochemistry. Further mechanistic analysis suggests the ET reaction of GOx shows a responsive correlation to the non‐ergodicity of those active GOx sites. A control experiment using pure FAD immobilized in the matrix doesn't show responses to glucose addition. 

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2. An Equipment-Free, Paper-Based Electrochemical Sensor for Visual Monitoring of Glucose Levels in Urine

   https://doi.org/10.1177/2472630319846876  

   Mohammadifar, Maedeh; Tahernia, Mehdi; Choi, Seokheun (May 2019, SLAS TECHNOLOGY: Translating Life Sciences Innovation)

   A novel electrochemical glucose sensor was created for a simple but semiquantitative visual screening of specific glucose concentrations in urine. This noninvasive glucose biosensor integrated a disposable, paper-based sensing strip and a simple amplifier circuit with a visual readout. The paper strip consisted of five enzyme-activated electrodes. Each electrode was connected to a specific indicator circuit that triggered a light-emitting diode (LED) when a predefined glucose concentration was reached. The device features (1) low-cost, disposable, paper-based glucose oxidase (GOx)/poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) sensing electrodes, (2) simple signal amplification, and (3) on-site, rapid, and visual detection. The sensor generated reliable, discrete visual responses to determine five glucose levels (1, 2, 3, 4, and higher than 4 mM) in urine in less than 2 min. This innovative approach will provide a simple but powerful glucose sensing paradigm for use in POC diagnostics. 

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3. Glucose‐Responsive Insulin and Delivery Systems: Innovation and Translation

   https://doi.org/10.1002/adma.201902004  

   Wang, Jinqiang; Wang, Zejun; Yu, Jicheng; Kahkoska, Anna_R; Buse, John_B; Gu, Zhen (August 2019, Advanced Materials)

   Abstract Type 1 and advanced type 2 diabetes treatment involves daily injections or continuous infusion of exogenous insulin aimed at regulating blood glucose levels in the normoglycemic range. However, current options for insulin therapy are limited by the risk of hypoglycemia and are associated with suboptimal glycemic control outcomes. Therefore, a range of glucose‐responsive components that can undergo changes in conformation or show alterations in intermolecular binding capability in response to glucose stimulation has been studied for ultimate integration into closed‐loop insulin delivery or “smart insulin” systems. Here, an overview of the evolution and recent progress in the development of molecular approaches for glucose‐responsive insulin delivery systems, a rapidly growing subfield of precision medicine, is presented. Three central glucose‐responsive moieties, including glucose oxidase, phenylboronic acid, and glucose‐binding molecules are examined in detail. Future opportunities and challenges regarding translation are also discussed. 

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4. Induced pluripotent stem cell-derived cells model brain microvascular endothelial cell glucose metabolism

   https://doi.org/10.1186/s12987-022-00395-z  

   Weber, Callie M.; Moiz, Bilal; Zic, Sophia M.; Alpízar Vargas, Viviana; Li, Andrew; Clyne, Alisa Morss (December 2022, Fluids and Barriers of the CNS)

   Abstract Glucose transport from the blood into the brain is tightly regulated by brain microvascular endothelial cells (BMEC), which also use glucose as their primary energy source. To study how BMEC glucose transport contributes to cerebral glucose hypometabolism in diseases such as Alzheimer’s disease, it is essential to understand how these cells metabolize glucose. Human primary BMEC (hpBMEC) can be used for BMEC metabolism studies; however, they have poor barrier function and may not recapitulate in vivo BMEC function. iPSC-derived BMEC-like cells (hiBMEC) are readily available and have good barrier function but may have an underlying epithelial signature. In this study, we examined differences between hpBMEC and hiBMEC glucose metabolism using a combination of dynamic metabolic measurements, metabolic mass spectrometry, RNA sequencing, and Western blots. hiBMEC had decreased glycolytic flux relative to hpBMEC, and the overall metabolomes and metabolic enzyme levels were different between the two cell types. However, hpBMEC and hiBMEC had similar glucose metabolism, including nearly identical glucose labeled fractions of glycolytic and TCA cycle metabolites. Treatment with astrocyte conditioned media and high glucose increased glycolysis in both hpBMEC and hiBMEC, though hpBMEC decreased glycolysis in response to fluvastatin while hiBMEC did not. Together, these results suggest that hiBMEC can be used to model cerebral vascular glucose metabolism, which expands their use beyond barrier models. 

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5. Insulin–Dendrimer Nanocomplex for Multi‐Day Glucose‐Responsive Therapy in Mice and Swine

   https://doi.org/10.1002/adma.202308965  

   Xian, Sijie; Xiang, Yuanhui; Liu, Dongping; Fan, Bowen; Mitrová, Katarína; Ollier, Rachel C.; Su, Bo; Alloosh, Muhammad Ali; Jiráček, Jiří; Sturek, Michael; et al (February 2024, Advanced Materials)

   Abstract The management of diabetes in a manner offering autonomous insulin therapy responsive to glucose‐directed need, and moreover with a dosing schedule amenable to facile administration, remains an ongoing goal to improve the standard of care. While basal insulins with reduced dosing frequency, even once‐weekly administration, are on the horizon, there is still no approved therapy that offers glucose‐responsive insulin function. Herein, a nanoscale complex combining both electrostatic‐ and dynamic‐covalent interactions between a synthetic dendrimer carrier and an insulin analogue modified with a high‐affinity glucose‐binding motif yields an injectable insulin depot affording both glucose‐directed and long‐lasting insulin availability. Following a single injection, it is even possible to control blood glucose for at least one week in diabetic swine subjected to daily oral glucose challenges. Measurements of serum insulin concentration in response to challenge show increases in insulin corresponding to elevated blood glucose levels, an uncommon finding even in preclinical work on glucose‐responsive insulin. Accordingly, the subcutaneous nanocomplex that results from combining electrostatic‐ and dynamic‐covalent interactions between a modified insulin and a synthetic dendrimer carrier affords a glucose‐responsive insulin depot for week‐long control following a single routine injection. 

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