For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
83
views
65
references
 Top references
cited by
36
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
2 collections
    0
    shares
      15
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Optical control of insulin release using a photoswitchable sulfonylurea

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Sulfonylureas are widely prescribed for the treatment of type 2 diabetes mellitus (T2DM). Through their actions on ATP-sensitive potassium (K ATP) channels, sulfonylureas boost insulin release from the pancreatic beta cell mass to restore glucose homeostasis. A limitation of these compounds is the elevated risk of developing hypoglycemia and cardiovascular disease, both potentially fatal complications. Here, we describe the design and development of a photoswitchable sulfonylurea, JB253, which reversibly and repeatedly blocks K ATP channel activity following exposure to violet-blue light. Using in situ imaging and hormone assays, we further show that JB253 bestows light sensitivity upon rodent and human pancreatic beta cell function. Thus, JB253 enables the optical control of insulin release and may offer a valuable research tool for the interrogation of K ATP channel function in health and T2DM.

          Abstract

          Sulfonylureas are widely used anti-diabetic drugs, which promote insulin release by blocking a pancreatic ion channel. Here the authors create a photoswitchable sulfonylurea derivative and use it to control insulin release from cultured cells and isolated pancreatic islets by illumination with blue light.

          Related collections

          Most cited references65

          • Record: found
          • Abstract: found
          • Article: not found

          A short history of SHELX

          George M. Sheldrick (2008)
          An account is given of the development of the SHELX system of computer programs from SHELX -76 to the present day. In addition to identifying useful innovations that have come into general use through their implementation in SHELX , a critical analysis is presented of the less-successful features, missed opportunities and desirable improvements for future releases of the software. An attempt is made to understand how a program originally designed for photographic intensity data, punched cards and computers over 10000 times slower than an average modern personal computer has managed to survive for so long. SHELXL is the most widely used program for small-molecule refinement and SHELXS and SHELXD are often employed for structure solution despite the availability of objectively superior programs. SHELXL also finds a niche for the refinement of macromolecules against high-resolution or twinned data; SHELXPRO acts as an interface for macromolecular applications. SHELXC , SHELXD and SHELXE are proving useful for the experimental phasing of macromolecules, especially because they are fast and robust and so are often employed in pipelines for high-throughput phasing. This paper could serve as a general literature citation when one or more of the open-source SHELX programs (and the Bruker AXS version SHELXTL ) are employed in the course of a crystal-structure determination.
          Article 0 comments Cited 1619 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            SIR97: a new tool for crystal structure determination and refinement

            Angela Altomare, Maria Burla, Mercedes Camalli … (1999)
            Article 0 comments Cited 574 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group.

              R C Turner, C A Cull, V Frighi … (1999)
              Treatment with diet alone, insulin, sulfonylurea, or metformin is known to improve glycemia in patients with type 2 diabetes mellitus, but which treatment most frequently attains target fasting plasma glucose (FPG) concentration of less than 7.8 mmol/L (140 mg/dL) or glycosylated hemoglobin A1c (HbA1c) below 7% is unknown. To assess how often each therapy can achieve the glycemic control target levels set by the American Diabetes Association. Randomized controlled trial conducted between 1977 and 1997. Patients were recruited between 1977 and 1991 and were followed up every 3 months for 3, 6, and 9 years after enrollment. Outpatient diabetes clinics in 15 UK hospitals. A total of 4075 patients newly diagnosed as having type 2 diabetes ranged in age between 25 and 65 years and had a median (interquartile range) FPG concentration of 11.5 (9.0-14.4) mmol/L [207 (162-259) mg/dL], HbA1c levels of 9.1% (7.5%-10.7%), and a mean (SD) body mass index of 29 (6) kg/m2. After 3 months on a low-fat, high-carbohydrate, high-fiber diet, patients were randomized to therapy with diet alone, insulin, sulfonylurea, or metformin. Fasting plasma glucose and HbA1c levels, and the proportion of patients who achieved target levels below 7% HbA1c or less than 7.8 mmol/L (140 mg/dL) FPG at 3, 6, or 9 years following diagnosis. The proportion of patients who maintained target glycemic levels declined markedly over 9 years of follow-up. After 9 years of monotherapy with diet, insulin, or sulfonylurea, 8%, 42%, and 24%, respectively, achieved FPG levels of less than 7.8 mmol/L (140 mg/dL) and 9%, 28%, and 24% achieved HbA1c levels below 7%. In obese patients randomized to metformin, 18% attained FPG levels of less than 7.8 mmol/L (140 mg/dL) and 13% attained HbA1c levels below 7%. Patients less likely to achieve target levels were younger, more obese, or more hyperglycemic than other patients. Each therapeutic agent, as monotherapy, increased 2- to 3-fold the proportion of patients who attained HbA1c below 7% compared with diet alone. However, the progressive deterioration of diabetes control was such that after 3 years approximately 50% of patients could attain this goal with monotherapy, and by 9 years this declined to approximately 25%. The majority of patients need multiple therapies to attain these glycemic target levels in the longer term.
              Article 0 comments Cited 329 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Nat Commun
                Journal ID (iso-abbrev): Nat Commun
                Title: Nature Communications
                Publisher: Nature Pub. Group
                ISSN (Electronic): 2041-1723
                Publication date (Electronic): 14 October 2014
                Volume: 5
                Electronic Location Identifier: 5116
                Affiliations
                [1 ]Department of Chemistry, Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein Science , Butenandtstrasse 5-13, 81377 München, Germany
                [2 ]Division of Biosciences, Department of Neuroscience, Physiology and Pharmacology, University College London , London WC1E 6BT, UK
                [3 ]Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa , 56126 Pisa, Italy
                [4 ]Clinical Islet Laboratory and Clinical Islet transplant program, University of Alberta , Edmonton, Alberta T6G 2C8, Canada
                [5 ]Section of Cell Biology, Department of Medicine, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Hospital, Du Cane Road , London W12 0NN, UK
                Author notes
                Article
                Publisher Item ID: ncomms6116
                DOI: 10.1038/ncomms6116
                PMC ID: 4208094
                PubMed ID: 25311795
                SO-VID: 3bfdb72f-95e4-4040-83cd-62a8e564567e
                Copyright © Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
                License:

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                Date received : 23 February 2014
                Date accepted : 01 September 2014
                Categories
                Subject: Article

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

                Comments

                Comment on this article

                scite_

                Similar content15

                See all similar

                Cited by34

                See all cited by

                Most referenced authors1,616

                See all reference authors