المؤلفون: Yufen Xiao, Jiamin Zhang, Tong Wu, Shuai Chen, Zhixiong Huang, Jianzhong Du

مصطلحات موضوعية: Biochemistry, Genetics, Pharmacology, Biotechnology, Science Policy, Chemical Sciences not elsewhere classified, phenylboronic acid derivative, pba either randomly, open new avenues, modulating molecule levels, may provide guidance, exhibits excellent long, bgl regulating efficacy, >- acryloyl glucosamine, statistical copolymer structure, reversible sugar substituting, longest effective sugar, acrylamidophenylboronic acid -<, regulate glucose levels, better glucose responsiveness, >- aga )], >- p, molecular structure, pcl -<, glucose modulator, glucose according, stat <, smartly take, regulation time, natural modulators

الوصف: Natural modulators, such as insulin, play a significant role in modulating molecule levels. Inspired by the role of natural modulators, herein, we propose a glucose modulator that is composed of a glycopolymersome only to regulate glucose levels. This insulin- and drug-free strategy can smartly take in and snap out glucose according to the surrounding blood glucose levels (BGLs) by reversible sugar substituting. The glycopolymersome is self-assembled from a biodegradable glycopolymer that is composed of sugar and phenylboronic acid derivative, poly(ε-caprolactone)- block -poly[(3-acrylamidophenylboronic acid- stat - N -acryloyl glucosamine] [PCL- b -P(AAPBA- stat -AGA)]. It exhibits excellent long-term hypoglycemic effects toward type 1 diabetic mice for at least 3 days upon one shot without observed side effects, which is the longest effective sugar-regulation time for the insulin and drug-free strategy. Most notably, we explored the effect of the molecular structure of the glycopolymers on the BGL regulating efficacy, where the glucosyl moiety was polymerized with PBA either randomly or separately. Block-statistical glycopolymersomes exhibited lower binding energy to glucose, better glucose responsiveness, and prolonged hypoglycemic effect due to the abundant intramolecular and intermolecular dynamic covalent bonds between AAPBA and AGA. Our finding confirmed the importance of a block-statistical copolymer structure and the key role of sugar in regulating BGLs without involving medication, which may provide guidance and open new avenues for design blood glucose regulating materials.

العلاقة: https://figshare.com/articles/journal_contribution/Three-Day_Blood_Glucose_Control_via_a_Glucose_Modulator_of_Glycopolymersome_Sugar_versus_Sugar/25070519Test

الإتاحة: https://doi.org/10.1021/acs.chemmater.3c03140.s001Test

المؤلفون: Satoshi Yoshino, Emi Ishida, Kazuhiko Horiguchi, Shunichi Matsumoto, Yasuyo Nakajima, Atsushi Ozawa, Masanobu Yamada, Eijiro Yamada

المصدر: International Journal of Molecular Sciences, Vol 25, Iss 9, p 4704 (2024)

مصطلحات موضوعية: diabetes, beta cells, glucose responsiveness, MLL, SLC2A1, SLC2A2, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: The escalating prevalence of diabetes mellitus underscores the need for a comprehensive understanding of pancreatic beta cell function. Interest in glucose effectiveness has prompted the exploration of novel regulatory factors. The myeloid/lymphoid or mixed-lineage leukaemia gene (MLL) is widely recognised for its role in leukemogenesis and nuclear regulatory mechanisms through its histone methyltransferase activity in active chromatin. However, its function within pancreatic endocrine tissues remains elusive. Herein, we unveil a novel role of MLL in glucose metabolism and insulin secretion. MLL knockdown in βHC-9 pancreatic beta cells diminished insulin secretion in response to glucose loading, paralleled by the downregulation of the glucose-sensitive genes SLC2a1 and SLC2a2. Similar observations were made in MLL heterozygous knockout mice (MLL+/−), which exhibited impaired glucose tolerance and reduced insulin secretion without morphological anomalies in pancreatic endocrine cells. The reduction in insulin secretion was independent of changes in beta cell mass or insulin granule morphology, suggesting the regulatory role of MLL in glucose-sensitive gene expression. The current results suggest that MLL interacts with circadian-related complexes to modulate the expression of glucose transporter genes, thereby regulating glucose sensing and insulin secretion. Our findings shed light on insulin secretion control, providing potential avenues for therapeutics against diabetes.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/25/9/4704Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/0726925ca76a4b4084b328505b3b4882Test

المؤلفون: Tan, Guohongfang, Jiang, Fujian, Jia, Tianshuo, Qi, Zhenzhen, Xing, Tieling, Kundu, Subhas C, Lu, Shenzhou

مصطلحات موضوعية: Silk, Microneedles, Glucose responsiveness, Insulin, Diabetes, Science & Technology

الوصف: Microneedles (MNs) have attracted great interest as a drug delivery alternative to subcutaneous injections for treating diabetes mellitus. We report MNs prepared from polylysine-modified cationized silk fibroin (SF) for responsive transdermal insulin delivery. Scanning electron microscopy analysis of MNs’ appearance and morphology revealed that the MNs were well arranged and formed an array with 0.5 mm pitch, and the length of single MNs is approximately 430 μm. The average breaking force of an MN is above 1.25 N, which guarantees that it can pierce the skin quickly and reach the dermis. Cationized SF MNs are pH-responsive. MNs dissolution rate increases as pH decreases and the rate of insulin release are accelerated. The swelling rate reached 223% at pH = 4, while only 172% at pH = 9. After adding glucose oxidase, cationized SF MNs are glucose-responsive. As the glucose concentration increases, the pH inside the MNs decreases, the MNs’ pore size increases, and the insulin release rate accelerates. In vivo experiments demonstrated that in normal Sprague Dawley (SD) rats, the amount of insulin released within the SF MNs was significantly smaller than that in diabetic rats. Before feeding, the blood glucose (BG) of diabetic rats in the injection group decreased rapidly to 6.9 mmol/L, and the diabetic rats in the patch group gradually reduced to 11.7 mmol/L. After feeding, the BG of diabetic rats in the injection group increased rapidly to 33.1 mmol/L and decreased slowly, while the diabetic rats in the patch group increased first to 21.7 mmol/L and then decreased to 15.3 mmol/L at 6 h. This demonstrated that the insulin inside the microneedle was released as the blood glucose concentration increased. Cationized SF MNs are expected to replace subcutaneous injections of insulin as a new modality for diabetes treatment. ; National Natural Science Foundation of China (Grant No. 51973144), College Nature Science Research Project of Jiangsu Province, China (Grant No. 20KJA540002), PAPD and Six Talent Peaks Project in ...

وصف الملف: application/pdf

العلاقة: https://www.mdpi.com/2313-7673/8/1/50Test; Tan,G.; Jiang,F.; Jia,T.; Qi, Z.; Xing,T.; Kundu,S.C.; Lu,S. Glucose-Responsive Silk Fibroin Microneedles for Transdermal Delivery of Insulin. Biomimetics 2023, 8,50.https://doi.org/10.3390Test/ biomimetics8010050; https://hdl.handle.net/1822/86760Test

الإتاحة: https://doi.org/10.3390/biomimetics8010050Test
https://hdl.handle.net/1822/86760Test

المؤلفون: Guohongfang Tan, Fujian Jiang, Tianshuo Jia, Zhenzhen Qi, Tieling Xing, Subhas C. Kundu, Shenzhou Lu

المصدر: Biomimetics; Volume 8; Issue 1; Pages: 50

مصطلحات موضوعية: silk, microneedles, glucose responsiveness, insulin, diabetes

الوصف: Microneedles (MNs) have attracted great interest as a drug delivery alternative to subcutaneous injections for treating diabetes mellitus. We report MNs prepared from polylysine-modified cationized silk fibroin (SF) for responsive transdermal insulin delivery. Scanning electron microscopy analysis of MNs’ appearance and morphology revealed that the MNs were well arranged and formed an array with 0.5 mm pitch, and the length of single MNs is approximately 430 μm. The average breaking force of an MN is above 1.25 N, which guarantees that it can pierce the skin quickly and reach the dermis. Cationized SF MNs are pH-responsive. MNs dissolution rate increases as pH decreases and the rate of insulin release are accelerated. The swelling rate reached 223% at pH = 4, while only 172% at pH = 9. After adding glucose oxidase, cationized SF MNs are glucose-responsive. As the glucose concentration increases, the pH inside the MNs decreases, the MNs’ pore size increases, and the insulin release rate accelerates. In vivo experiments demonstrated that in normal Sprague Dawley (SD) rats, the amount of insulin released within the SF MNs was significantly smaller than that in diabetic rats. Before feeding, the blood glucose (BG) of diabetic rats in the injection group decreased rapidly to 6.9 mmol/L, and the diabetic rats in the patch group gradually reduced to 11.7 mmol/L. After feeding, the BG of diabetic rats in the injection group increased rapidly to 33.1 mmol/L and decreased slowly, while the diabetic rats in the patch group increased first to 21.7 mmol/L and then decreased to 15.3 mmol/L at 6 h. This demonstrated that the insulin inside the microneedle was released as the blood glucose concentration increased. Cationized SF MNs are expected to replace subcutaneous injections of insulin as a new modality for diabetes treatment.

وصف الملف: application/pdf

العلاقة: Biomimetics of Materials and Structures; https://dx.doi.org/10.3390/biomimetics8010050Test

الإتاحة: https://doi.org/10.3390/biomimetics8010050Test

المؤلفون: Nai-Pin Lin, Nan Zheng, Landa Purushottam, Yi Wolf Zhang, Danny Hung-Chieh Chou

المصدر: Frontiers in Chemistry, Vol 10 (2022)

مصطلحات موضوعية: insulin, glucose responsiveness, peptide, insulin modification, phenylboronate, Chemistry, QD1-999

الوصف: Glucose-responsive insulin represents a promising approach to regulate blood glucose levels. We previously showed that attaching two fluorophenylboronic acid (FPBA) residues to the C-terminal B chain of insulin glargine led to glucose-dependent solubility. Herein, we demonstrated that relocating FPBA from B chain to A chain increased the baseline solubility without affecting its potency. Furthermore, increasing the number of FPBA groups led to increased glucose-dependent solubility.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fchem.2022.859133/fullTest; https://doaj.org/toc/2296-2646Test

الوصول الحر: https://doaj.org/article/22cb8c0690774d3f9270ef7e8ec302b6Test

المؤلفون: Sarah Duin, Shreya Bhandarkar, Susann Lehmann, Elisabeth Kemter, Eckhard Wolf, Michael Gelinsky, Barbara Ludwig, Anja Lode

المصدر: Biomedicines; Volume 10; Issue 6; Pages: 1420

مصطلحات موضوعية: 3D bioprinting, alginate-methylcellulose, neonatal porcine islet-like cell clusters, functionality, glucose-responsiveness

الوصف: The transplantation of pancreatic islets can prevent severe long-term complications in diabetes mellitus type 1 patients. With respect to a shortage of donor organs, the transplantation of xenogeneic islets is highly attractive. To avoid rejection, islets can be encapsulated in immuno-protective hydrogel-macrocapsules, whereby 3D bioprinted structures with macropores allow for a high surface-to-volume ratio and reduced diffusion distances. In the present study, we applied 3D bioprinting to encapsulate the potentially clinically applicable neonatal porcine islet-like cell clusters (NICC) in alginate-methylcellulose. The material was additionally supplemented with bovine serum albumin or the human blood plasma derivatives platelet lysate and fresh frozen plasma. NICC were analysed for viability, proliferation, the presence of hormones, and the release of insulin in reaction to glucose stimulation. Bioprinted NICC are homogeneously distributed, remain morphologically intact, and show a comparable viability and proliferation to control NICC. The number of insulin-positive cells is comparable between the groups and over time. The amount of insulin release increases over time and is released in response to glucose stimulation over 4 weeks. In summary, we show the successful bioprinting of NICC and could demonstrate functionality over the long-term in vitro. Supplementation resulted in a trend for higher viability, but no additional benefit on functionality was observed.

وصف الملف: application/pdf

العلاقة: Biomedical Engineering in Human Health; https://dx.doi.org/10.3390/biomedicines10061420Test

الإتاحة: https://doi.org/10.3390/biomedicines10061420Test

المؤلفون: Duin, S., Bhandarkar, S., Lehmann, S., Kemter, E., Wolf, E., Gelinsky, M., Ludwig, B., Lode, A.

المصدر: Biomedicines 10:1420 (2022)

مصطلحات موضوعية: 3d Bioprinting, Alginate-methylcellulose, Functionality, Glucose-responsiveness, Neonatal Porcine Islet-like Cell Clusters

الوصف: The transplantation of pancreatic islets can prevent severe long-term complications in diabetes mellitus type 1 patients. With respect to a shortage of donor organs, the transplantation of xenogeneic islets is highly attractive. To avoid rejection, islets can be encapsulated in immuno-protective hydrogel-macrocapsules, whereby 3D bioprinted structures with macropores allow for a high surface-to-volume ratio and reduced diffusion distances. In the present study, we applied 3D bioprinting to encapsulate the potentially clinically applicable neonatal porcine islet-like cell clusters (NICC) in alginate-methylcellulose. The material was additionally supplemented with bovine serum albumin or the human blood plasma derivatives platelet lysate and fresh frozen plasma. NICC were analysed for viability, proliferation, the presence of hormones, and the release of insulin in reaction to glucose stimulation. Bioprinted NICC are homogeneously distributed, remain morphologically intact, and show a comparable viability and proliferation to control NICC. The number of insulin-positive cells is comparable between the groups and over time. The amount of insulin release increases over time and is released in response to glucose stimulation over 4 weeks. In summary, we show the successful bioprinting of NICC and could demonstrate functionality over the long-term in vitro. Supplementation resulted in a trend for higher viability, but no additional benefit on functionality was observed.

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35740440; info:eu-repo/semantics/altIdentifier/wos/WOS:000818329200001; info:eu-repo/semantics/altIdentifier/isbn/2227-9059; info:eu-repo/semanti; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=65533Test; urn:isbn:2227-9059; urn:issn:2227-9059

الإتاحة: https://doi.org/10.3390/biomedicines10061420Test
https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=65533Test

المؤلفون: Theresa M. Reineke

المصدر: ACS macro letters. 5(1)

مصطلحات موضوعية: chemistry.chemical_classification, Materials science, Polymers and Plastics, Stimuli responsive, Glucose responsiveness, Organic Chemistry, Nanotechnology, 02 engineering and technology, Polymer, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, Inorganic Chemistry, Hydrolytic degradation, Tissue engineering, chemistry, Drug delivery, Materials Chemistry, 0210 nano-technology

الوصف: Responsive polymers with properties designed to interact with their surrounding environment are enabling “smart” design features for custom biomaterials. Numerous applications are being innovated, ranging from diagnostics and imaging to tissue engineering and drug delivery. Herein, I feature a collection of research articles published in ACS Macro Letters that highlight an array of innovative chemical attributes such as pH-triggered hydrolytic degradation, reduction-based release, photomodulation, glucose responsiveness, thermal sensitivity, and membrane permeating peptides. The chemical, physical, mechanical, and morphological properties of polymeric structures can be custom tailored to enhance numerous features such as biological delivery, pharmaceutical potency and safety, disease diagnosis, and antigen/biomaker detection.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::738539d1349d0ad017e553a80fd28f0aTest
https://pubmed.ncbi.nlm.nih.gov/35668593Test

المؤلفون: Chang Li, Yingli An, Juan Lv, Rujiang Ma, Xiaoyu Liu, Fan Huang, Linqi Shi

المصدر: ACS Applied Bio Materials. 3:1598-1606

مصطلحات موضوعية: medicine.medical_specialty, Polymeric micelles, Chemistry, Glucose responsiveness, Insulin, medicine.medical_treatment, Biochemistry (medical), Biomedical Engineering, Insulin delivery, General Chemistry, medicine.disease, Diabetes treatment, Biomaterials, chemistry.chemical_compound, Endocrinology, Internal medicine, Diabetes mellitus, medicine, Phenylboronic acid

الوصف: In the past decades, insulin delivery systems have been widely developed for diabetes treatment. Though a few works have investigated polymeric micelles with glucose and H2O2 dual-responsiveness fo...

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::d09e04333817a89c2c1655c9030422b4Test
https://doi.org/10.1021/acsabm.9b01185Test

المؤلفون: Carolyn R. Cho, Bhargava Kandala, Craig Fancourt, Sandra A.G. Visser, Alexander W. Krug

المصدر: Clinical Pharmacology and Therapeutics

مصطلحات موضوعية: Blood Glucose, medicine.medical_treatment, Decision Making, Computational biology, Models, Biological, 030226 pharmacology & pharmacy, Glucose responsive, 03 medical and health sciences, 0302 clinical medicine, Drug Development, Drug Discovery, Tutorial, Diabetes Mellitus, Animals, Humans, Hypoglycemic Agents, Insulin, Medicine, Computer Simulation, Pharmacology (medical), Pharmacology, Drug discovery, business.industry, Glucose responsiveness, Translational medicine, Clinical trial, Drug development, 030220 oncology & carcinogenesis, business, Non diabetic

الوصف: A model-informed drug discovery and development strategy played a key role in the novel glucose-responsive insulin MK-2640's early clinical development strategy and supported a novel clinical trial paradigm to assess glucose responsiveness. The development and application of in silico modeling approaches by leveraging substantial published clinical insulin pharmacokinetic-pharmacodynamic (PKPD) data and emerging preclinical and clinical data enabled rapid quantitative decision making. Learnings can be applied to define PKPD properties of novel insulins that could become therapeutically meaningful for diabetic patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::153380340c63932bd8745f0ccef033beTest
https://doi.org/10.1002/cpt.1729Test