Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We demonstrate a colorimetric glucose recognition material consisting of a crystalline colloidal array embedded within a polyacrylamide-poly(ethylene glycol) (PEG) hydrogel, or a polyacrylamide-15-crown-5 hydrogel, with pendent phenylboronic acid groups. We utilize a new molecular recognition motif, in which boronic acid and PEG (or crown ether) functional groups are prepositioned in a photonic crystal hydrogel, such that glucose self-assembles these functional groups into a supramolecular complex. The formation of the complex results in an increase in the hydrogel cross-linking, which for physiologically relevant glucose concentration blue shifts the photonic crystal diffraction. The visually evident diffraction color shifts across the visible spectral region over physiologically important glucose concentration ranges. These materials respond to glucose at physiological ionic strengths and pH values and are selective in their mode of response for glucose over galactose, mannose, and fructose. Thus, we have developed a new recognition motif for glucose that shows promise for the fabrication of noninvasive or minimally invasive in vivo glucose sensing for patients with diabetes mellitus.
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PMID:High ionic strength glucose-sensing photonic crystal. 1291 72

This study is devoted to the development of novel glucose-responsive polymers that operate under physiological conditions (pH 7.4, 37 degrees C), aiming for future use in a self-regulated insulin delivery system to treat diabetes mellitus. The approach involves the use of a newly synthesized phenylborate derivative [4-(1,6-dioxo-2,5-diaza-7-oxamyl) phenylboronic acid, DDOPBA] possessing an appreciably low pK(a) ( approximately 7.8) as a glucose-sensing moiety, as well as the adoption of poly(N-isopropylmethacrylamide), PNIPMAAm, as the main chain that exhibits critical solution behavior in the range close to physiological temperature. Glucose- and pH-dependent changes in the critical solution behavior of the resultant copolymers were investigated at varying temperatures, revealing definite glucose sensitivities near the physiological conditions. Furthermore, DDOPBA moieties in the copolymers maintained constant apparent pK(a) values even when the temperature approaches the critical solution points of the main chain, indicating that spacing of the phenylborate moiety from the polymer backbone is a feasible way to minimize the microenvironment effect caused by a temperature-induced change in the hydration state of the polymer strands.
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PMID:Glucose-responsive polymer bearing a novel phenylborate derivative as a glucose-sensing moiety operating at physiological pH conditions. 1295 13

In this paper, we report on the design and characterization of a new hydrogel-based implantable wireless glucose sensor. The basic device structure is a passive [inductor/capacitor (LC)] micromachined resonator coupled to a stimuli-sensitive hydrogel, which is confined between a stiff nanoporous membrane and a thin glass diaphragm. As glucose molecules pass through the nanoporous membrane, the hydrogel swells and deflects the flexible glass diaphragm, which is the movable plate of the variable capacitor in the totally integrated passive LC resonator. The corresponding change in resonant frequency can be remotely detected. A glucose- sensitive phenylboronic acid-based hydrogel was loaded into the microtransponder, and its sensitivity and time response were measured. Prior to hydrogel loading, the sensitivity of the pressure sensor to applied air pressure was measured to be -222 kHz/kPa over the frequency range 51-->42 MHz. The sensor showed a sensitivity of -34.3 kHz/mM over the glucose concentration range 0-20 mM (at pH 7.4), and a response time of 90 min. The dynamic response, although unacceptable at such values, can be easily improved by decreasing the hydrogel thickness and reducing the sensor and porous membrane thicknesses. The transponder's overall dimensions were 5x5x0.8 mm3, small enough for subcutaneous implantation.
Diabetes Technol Ther 2006 Feb
PMID:A hydrogel-based implantable micromachined transponder for wireless glucose measurement. 1647 58

The complexity of the human plasma proteome is greatly increased by post-translational modifications. Besides physiological modifications, pathological conditions such as diabetes are responsible for adding to this complexity by producing advanced glycation endproducts (AGEs). When searching for specific biomarkers it is a prerequisite to reduce this complexity prior to analysis. To do this, agarose hydrogel was used to create a high-capacity affinity layer on the modified aluminum surface of MALDI (matrix-assisted laser desorption/ionization) targets. 3-Aminophenylboronic acid was immobilized via cyanogen bromide activation as a ligand for affinity sorption of glycated proteins, followed by their direct detection by MALDI. High protein capacity of prepared MALDI chips, efficient separation and low non-specific protein binding were demonstrated. The results show that phenylboronic acid modified hydrogels are very suitable for creating affinity surfaces for the high-throughput analysis of AGEs.
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PMID:Application of phenylboronic acid modified hydrogel affinity chips for high-throughput mass spectrometric analysis of glycated proteins. 1712 56

Alternations of sialic acid (SA) content on cell surface glycan chains have been implicated in numerous normal and pathological processes including developments, differentiations, and tumor metastasis. Overexpressions of SA have been implicated in the malignant and metastatic phenotypes for many different types of cancers, while decreased SA expression has also been identified in erythrocytes of diabetic mellitus. Techniques to conveniently monitor cell surface SA would therefore have great relevance to cytology. Preexisting methodologies to quantify SA, however, involve multiple enzymatic, dye-labeling, and lethal procedures, which are costly and time-consuming. Here we developed a potentiometric SA detection using a phenylboronic acid (PBA) compound integrated into the form of a self-assembled monolayer (SAM) onto a field effect transistor (FET) extended gold gate electrode. Due to selective binding between undisassociated PBA and SA at pH 7.4 among other glycan chain constituent monosaccharides, we found that carboxyl anions of SA were exclusively detectable as the change in threshold voltage (V(T)) of the PBA-modified FET. The technique was applied to analyses of altered SA expressions on rabbit erythrocyte as a model for diabetes. Comparative SA expression analyses for each healthy and diseased model revealed that the disease could be feasibly diagnosed simply by placing the known-count cell suspensions onto the device without any labeling and enzymatic procedures. Such a technique may also provide a quantitative adjunct to histological evaluation of tumor malignancy and metastatic potential during intra- and postoperative diagnoses. Also advantageously, a technique herein described is all within a CMOS (Complementary Metal Oxide Semiconductor) compatible format thus promising for highly efficient and low cost manufacturing with readiness of downsizing and integration by virtue of advanced semiconductor processing technologies.
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PMID:Noninvasive sialic acid detection at cell membrane by using phenylboronic acid modified self-assembled monolayer gold electrode. 1966 94

The incorporation of the specialized carbohydrate affinity ligand methacrylamido phenylboronic acid in polyacrylamide gels for SDS-PAGE analysis has been successful for the separation of carbohydrates and has here been adapted for the analysis of post-translationally modified proteins. While conventional SDS-PAGE analysis cannot distinguish between glycated and unglycated proteins, methacrylamido phenylboronate acrylamide gel electrophoresis (mP-AGE) in low loading shows dramatic retention of delta-gluconolactone modified proteins, while the mobility of the unmodified proteins remains unchanged. With gels containing 1% methacrylamido phenylboronate, mP-AGE analysis of gluconoylated recombinant protein Sbi results in the retention of the modified protein at a position expected for a protein that has quadrupled its expected molecular size. Subsequently, mP-AGE was tested on HSA, a protein that is known to undergo glycation under physiological conditions. mP-AGE could distinguish between various carbohydrate-protein adducts, using in vitro glycated HSA, and discriminate early from late glycation states of the protein. Enzymatically glycosylated proteins show no altered retention in the phenylboronate-incorporated gels, rendering this method highly selective for glycated proteins. We reveal that a trident interaction between phenylboronate and the Amadori cis 1,2 diol and amine group provides the molecular basis of this specificity. These results epitomize mP-AGE as an important new proteomics tool for the detection, separation, visualization and identification of protein glycation. This method will aid the design of inhibitors of unwanted carbohydrate modifications in recombinant protein production, ageing, diabetes, cardiovascular diseases and Alzheimer's disease.
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PMID:Analysis of protein glycation using phenylboronate acrylamide gel electrophoresis. 1989 78

Here described is a phenylboronic acid (PBA) based glucose-responsive hydrogel operating under physiological pH and temperature, a material potentially applicable to a totally synthetic smart insulin delivery system to treat diabetes.
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PMID:A totally synthetic glucose responsive gel operating in physiological aqueous conditions. 2023 6

The quantitative analysis of sialic acid (SA) at an erythrocyte membrane is becoming an important clinical parameter in diagnosing cancer and diabetes. In spite of such clinical importance, there are only a few, very expensive, time consuming and complicated quantifying methods established. To solve this problem, we demonstrate a novel and direct measurement technique for SA exposed to the cell membrane using a photothermal biosensing system in which the hemoglobin molecules in the erythrocyte absorb a specific wavelength of photons (532 nm) and convert it to a temperature change. For measuring the quantity of SA, we first modified the sensor surface of a micro-scaled thermometer using phenylboronic acid (PBA) containing a self-assembled monolayer (SAM) to capture the SA-expressing erythrocytes. Second, the sensor surface was thoroughly washed, and when more SA was expressed, tighter association of erythrocytes to the biosensor was expected. Thirdly, blood sample changes in temperature, heated by the 532 nm wavelength laser, were measured by the bottom layer's micron sized platinum thermometer. The temperature changes from the erythrocytes captured on the sensor surface could be estimated by the amount of SA expressed on the erythrocyte membrane. This novel SA analysis system can solve the problems raised by conventional methods such as multiple enzyme reactions and a time consuming process. We expect that this system will help provide a new tool in the quantitative analysis of SA expression level for the diagnosis of diabetes and cancers.
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PMID:Quantitative analysis of sialic acid on erythrocyte membranes using a photothermal biosensor. 2246 47

Polymeric nanoparticles with glucose-responsiveness under physiological conditions are of great interests in developing drug delivery system for the treatment of diabetes. Herein, glucose-responsive complex micelles were prepared by self-assembly of a phenylboronic acid-contained block copolymer PEG-b-P(AA-co-APBA) and a glycopolymer P(AA-co-AGA) based on the covalent complexation between phenylboronic acid and glycosyl. The formation of the complex micelles with a P(AA-co-APBA)/P(AA-co-AGA) core and a PEG shell was confirmed by HNMR analysis. The glucose-responsiveness of the complex micelles was investigated by monitoring the light scattering intensity and the fluorescence (ARS) of the micelle solutions. The complex micelles displayed an enhanced glucose-responsiveness compared to the simple PEG-b-P(AA-co-APBA) micelles and the sensitivity of the complex micelles to glucose increased with the decrease of the amount of P(AA-co-AGA) in the compositions. The cytotoxicity of the polymers and the complex micelles was also evaluated by MTT assay. This kind of complex micelles may be an excellent candidate for insulin delivery and may find application in the treatment of diabetes.
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PMID:Phenylboronic acid-based complex micelles with enhanced glucose-responsiveness at physiological pH by complexation with glycopolymer. 2295 42

We report a potentiometric method for measuring the hemoglobin A1c (HbA1c, glycated hemoglobin) concentration, hemoglobin (Hb) concentration, and percent HbA1c (%HbA1c) in human blood hemolysate. The %HbA1c is important for diagnosis and management of diabetes mellitus. Alizarin red s (ARS) is used as a redox indicator. Phenylboronic acid (PBA) binds to both ARS and HbA1c via diol-boronic acid complexation. The binding of PBA to ARS shifts its redox potential negatively. However, when HbA1c competes with ARS for PBA binding, the solution potential shifts positively. This shift is linked to the HbA1c concentration. The concentration of Hb is determined by allowing it to react with Fe(CN)(6)(3-). The potential shift arising from the reduction of Fe(CN)(6)(3-) by Hb is proportional to the logarithm of the Hb concentration. The results obtained for %HbA1c in human blood hemolysate are in good agreement with those determined using a reference method.
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PMID:Determination of percent hemoglobin A1c using a potentiometric method. 2325 36


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