Preparation and properties of poly(ethylene glycol)-bpoly( 3-acrylamidophenylboronic acid) glucose responsive particles and their hyaluronic acid-based microneedle patches

To overcome the pain and risk of hypoglycemia in insulin administration,glucose-responsive microneedles have been developed by researchers,which could release insulin according to the blood glucose level.We designed a kind of particles by a reversible addition-fragmentation chain transfer(RAFT)method containing a phenylboronic acid group as the sensor of glucose and carrier of insulin.poly(ethylene glycol)(PEG)-2-(dodecylthio(thiocarbonyl)thio)-2-methylpropionic acid(DDMAT)was synthesized as a macromolecular RAFT agent,which was then reacted with 3-acrylamidophenylboronic acid(AAPBA)to synthesize the block copolymer PEG-b-PAAPBA.Glucose-responsive particles loaded with insulin were prepared by self-assembly based on hydrophilic-hydrophobic interactions.Microneedle patches loaded with glucose-responsive particles were prepared using hyaluronic acid as the substrate.The insulin release behavior of the particles in glucose solutions of 0,100,and 400 mg/dL showed significant glucose responsiveness and good biosafety.The results of blood glucose control experiments in rats indicate that a single microneedle patch can effectively maintain normal blood glucose for over 7 h.

Efficacy of a Diabetes Specific Nutritional Supplement (DSNS) on Glycemic Response in Prediabetic Adults: A Two-Armed, Open-Labelled Randomized Controlled Study

It is well known that Diabetes Specific Nutritional Supplements (DSNSs) are linked to improved glycemic control in individuals with diabetes. However, data on efficacy of DSNSs in prediabetics is limited. This was a two-armed, open-labelled, randomized controlled six-week study on 199 prediabetics [30 - 65 years;Glycosylated Hemoglobin (HbA1c) 5.7% - 6.4% and/or Fasting Blood Glucose (FBG) 100-125 mg/dl]. Two parallel phases were conducted: Acute Blood Glucose Response (ABGR) and Intervention phase. Prediabetic participants were randomized into test (n = 100) and control (n = 99). The primary objective was to assess the ABGR of DSNS versus an isocaloric snack, measured by incremental Area under the Curve (iAUC). Test and control received 60 g of DSNS and 56 g of isocaloric snack (cornflakes) respectively, both in 250 ml double-toned milk on visit days 1, 15, 29 and 43. Postprandial Blood Glucose (PPG) was estimated at 30, 60, 90, 120, 150 and 180 minutes. During the 4 weeks intervention phase, the test group received DSNS with lifestyle counselling (DSNS + LC) and was compared with the control receiving lifestyle counselling alone (LC alone). Impact was studied on FBG, HbA1C, anthropometry, body composition, blood pressure, nutrient intake, and physical activity. The impact of DSNS was also studied using CGM between two 14-day phases: CGM1 baseline (days 1 - 14) and CGM2 endline (days 28 - 42). DSNS showed significantly lower PPG versus isocaloric snack at 30 (p 12, and chromium were reported by DSNS + LC versus LC alone. No other significant changes were reported between groups. It may be concluded that DSNS may be considered as a snack for prediabetic or hyperglycemic individuals requiring nutritional support for improved glycemic control.

Transcriptional activation of glucose transporter 1 in orthodontic tooth movement-associated mechanical response

The interplay between mechanoresponses and a broad range of fundamental biological processes, such as cell cycle progression,growth and differentiation, has been extensively investigated. However, metabolic regulation in mechanobiology remains largely unexplored. Here, we identified glucose transporter 1(GLUT1)—the primary glucose transporter in various cells—as a novel mechanosensitive gene in orthodontic tooth movement(OTM). Using an in vivo rat OTM model, we demonstrated the specific induction of Glut1 proteins on the compressive side of a physically strained periodontal ligament. This transcriptional activation could be recapitulated in in vitro cultured human periodontal ligament cells(PDLCs), showing a time-and dose-dependent mechanoresponse. Importantly, application of GLUT1 specific inhibitor WZB117 greatly suppressed the efficiency of orthodontic tooth movement in a mouse OTM model, and this reduction was associated with a decline in osteoclastic activities. A mechanistic study suggested that GLUT1 inhibition affected the receptor activator for nuclear factor-κ B Ligand(RANKL)/osteoprotegerin(OPG)system by impairing compressive force-mediated RANKL upregulation. Consistently, pretreatment of PDLCs with WZB117 severely impeded the osteoclastic differentiation of co-cultured RAW264.7 cells. Further biochemical analysis indicated mutual regulation between GLUT1 and the MEK/ERK cascade to relay potential communication between glucose uptake and mechanical stress response. Together, these cross-species experiments revealed the transcriptional activation of GLUT1 as a novel and conserved linkage between metabolism and bone remodelling.

Responses to oral glucose challenge differ by physical activity volume and intensity: A pilot study

Background:One-hour postprandial hyperglycemia is associated with increased risk of type 2 diabetes and cardiovascular disease.Physical activity(PA)has short-term beneficial effects on post-meal glucose response.This study compared the oral glucose tolerance test results of 3 groups of people with habitually different levels of PA.Methods:Thirty-one adults without diabetes(age 25.9±6.6 years;body mass index 23.8±3.8 kg/m^2;mean±SD)were recruited and divided into 3 groups based on self-reported PA volume and intensity:low activity<30 min/day of moderate-intensity activity(n=11),moderately active≥30 min/day of moderate-intensity PA(n=10),and very active≥60 min/day of PA at high intensity(n=10).Participants completed an oral glucose tolerance test(50 g glucose)with capillary blood samples obtained at baseline,15 min,30 min,45 min,60 min,90 min,and 120 min post-ingestion.Results:There were no significant differences between groups for age or body fat percentage or glycated hemoglobin(p>0.05).The groups were significantly different in terms of baseline glucose level(p=0.003)and,marginally,for gender(p=0.053)and BMI(p=0.050).There was a statistically significant effect of PA on the 1-h postprandial glucose results(p=0.029),with differences between very active and low activity groups(p=0.008)but not between the moderately active and low activity groups(p=0.360),even when baseline glucose level and gender differences were accounted for.For incremental area under the curve there was no significant effect of activity group once gender and body fat percentage had been accounted for(p=0.401).Those in the low activity group took 15 min longer to reach peak glucose level than those in the very active group(p=0.012).Conclusion:The results suggest that high levels of PA have a beneficial effect on postprandial blood glucose profiles when compared to low and moderate levels of activity.

A novel hydrogel with glucose-responsive hyperglycemia regulation and antioxidant activity for enhanced diabetic wound repair

Enhanced diabetic wound repair remained a global challenge.Herein,we reported a novel hydrogel with glucose-responsive hyperglycemia regulation and antioxidant activity for enhanced diabetic wound repair.In this study,gallic acid(GA)with strong antioxidant activity was grafted onto chitosan(CS)chains by one-step synthesis,and then incorporated into poly(ethylene glycol)diacrylate(PEG-DA)hydrogel matrix to obtain a novel antioxidant hybrid hydrogel(PEG-DA/CS-GA).Meanwhile,polyethyleneimine(PEI)was modified with a unique glucose-sensitive phenylboronic acid(PBA)molecule to load insulin(PEIPBA/insulin nano-particles,PEI-PBA/insulin NPs),which could be immobilized in the PEG-DA/CS-GA hybrid hydrogel by the formation of dynamic borate bond between the phenylboronic acid groups on the PEI-PBA and the polyphenol groups on the CSGA.The results indicated that the PEG-DA/PEI-PBA/insulin/CS-GA(PPIC)hydrogel platform not only had remarkable biocompatibility,but also displayed extraordinary antioxidant properties(DPPH scavenging rate>95.0%),and effectively protected cells from oxidative damage(decreased MDA levels,increased Superoxide dismutase(SOD)levels and stable GSH/GSSG levels).Meanwhile,the PPIC hydrogel also exhibited unique glucose-responsive insulin release characteristics,and effectively regulated the blood glucose level.The in vitro and in vivo results demonstrated that our PPIC hydrogel could promoted angiogenesis(increased VEGF and CD 31 expression),reshaped the inflammatory microenvironment(decreased IL-6 and increased IL-10 level),and achieved wound closure within 20 days.All these results strongly indicated that the PPIC hydrogel represented a tough and efficient platform for diabetic wound treatment.

Smart polymers for the controlled delivery of drugs–a concise overview

Smart polymers have enormous potential in various applications.In particular,smart polymeric drug delivery systems have been explored as“intelligent”delivery systems able to release,at the appropriate time and site of action,entrapped drugs in response to specific physiological triggers.These polymers exhibit a non-linear response to a small stimulus leading to a macroscopic alteration in their structure/properties.The responses vary widely from swelling/contraction to disintegration.Synthesis of new polymers and crosslinkers with greater biocompatibility and better biodegradability would increase and enhance current applications.The most fascinating features of the smart polymers arise from their versatility and tunable sensitivity.The most significant weakness of all these external stimuli-sensitive polymers is slow response time.The versatility of polymer sources and their combinatorial synthesis make it possible to tune polymer sensitivity to a given stimulus within a narrow range.Development of smart polymer systems may lead to more accurate and programmable drug delivery.In this review,we discuss various mechanisms by which polymer systems are assembled in situ to form implanted devices for sustained release of therapeutic macromolecules,and we highlight various applications in the field of advanced drug delivery.

Cinnamomum zeylanicum and Curcuma longa incorporated dairy yoghurts with hindered glycaemic properties for healthy people

This study mainly compare glycaemic responses of a control yoghurt(typical dairy yoghurt)against two novel yoghurt products with added spices oleoresins(Cinnamon yoghurt-Cinnamomum zeylanicum,turmeric yoghurt-Curcuma longa)using 16 healthy volunteers in a randomized crossover study.Blood glucose concentrations were measured at fasting state and 30,45,60,90,120 min following the ingestion,using a Blood Glucose Monitoring System and blood glucose response curves were plotted.Nutritional and physicochemical properties were also compared and no significant differences(P>0.05)were observed between novel yoghurts and the control within the storage period.Significant reductions in peak blood glucose concentration and area under the curve(AUC)(P<0.05)for both novel products compared to standard dairy yoghurt was observed;revealing the reduction of glycaemic impact by spice ingredients.Peak reductions of glucose concentration for cinnamon yoghurt was 9.61%,for turmeric yoghurt was 9.26%;they were considerably lower compared to the control.Mean peak serum glucose concentration for control,cinnamon yoghurt and turmeric yoghurt were(113.38±6.39),(102.50±6.00),(102.88±5.38)mg/dL respectively and mean AUC were(11951±523),(11012±611),(10941±530)(mg/dL)·min respectively.Hence novel yoghurt products are proven to be excellent sources in reducing postprandial blood glucose responses.©2021 Beijing Academy of Food Sciences.yoghuart products sae proven to be excellent sources in reducing postprandial blood ghncose Tesponses.

Succinylation improves the slowly digestible starch fraction of cardaba banana starch. A process parameter optimization study

The study investigated the improvement of slowly digestible starch fraction of cardaba banana via octenyl succinic anhydride(OSA)modification process.A nonlinear(Response surface methodology[RSM]and artificial neural network[ANN])and linear(partial least square[PLS])modelswere employed and their predictabilitywas compared.The result revealed that all the modelling techniques were accurate in predicting the experimental process.The optimized RSM values for the production of slowly digestible starch(SDS)fraction were OSA concentration of 4%,reaction time of 47.49 min,and pH of 10 with a predicted SDS value of 44.64%.Among the modelling techniques,ANNwas adjudged as the predictivemodel for improving the SDS yield.The regression coefficient coupled with the variable important in the projection(VIP)values of the PLS model indicated that the OSA concentrationwas themost important factors responsible for high SDS yield.Finally,a structural comparison of the optimized starch against native starch revealed the formation of high ordered crystalline structure of the starch due to the impregnation of the modifying agent to the hydroxyl group of the cardaba banana starch.