The Experts below are selected from a list of 45 Experts worldwide ranked by ideXlab platform

S. Lenzen - One of the best experts on this subject based on the ideXlab platform.

  • The mechanisms of alloxan- and streptozotocin-induced diabetes
    Diabetologia, 2008
    Co-Authors: S. Lenzen
    Abstract:

    Alloxan and streptozotocin are toxic glucose analogues that preferentially accumulate in pancreatic beta cells via the GLUT2 glucose transporter. In the presence of intracellular thiols, especially glutathione, alloxan generates reactive oxygen species (ROS) in a cyclic redox reaction with its reduction product, Dialuric Acid. Autoxidation of Dialuric Acid generates superoxide radicals, hydrogen peroxide and, in a final iron-catalysed reaction step, hydroxyl radicals. These hydroxyl radicals are ultimately responsible for the death of the beta cells, which have a particularly low antioxidative defence capacity, and the ensuing state of insulin-dependent 'alloxan diabetes'. As a thiol reagent, alloxan also selectively inhibits glucose-induced insulin secretion through its ability to inhibit the beta cell glucose sensor glucokinase. Following its uptake into the beta cells, streptozotocin is split into its glucose and methylnitrosourea moiety. Owing to its alkylating properties, the latter modifies biological macromolecules, fragments DNA and destroys the beta cells, causing a state of insulin-dependent diabetes. The targeting of mitochondrial DNA, thereby impairing the signalling function of beta cell mitochondrial metabolism, also explains how streptozotocin is able to inhibit glucose-induced insulin secretion.

  • relative importance of cellular uptake and reactive oxygen species for the toxicity of alloxan and Dialuric Acid to insulin producing cells
    Free Radical Biology and Medicine, 2006
    Co-Authors: Matthias Elsner, Ewa Gurgulconvey, S. Lenzen
    Abstract:

    The diabetogenic agent alloxan is selectively accumulated in insulin-producing cells through uptake via the GLUT2 glucose transporter in the plasma membrane. In the presence of intracellular thiols, especially glutathione, alloxan generates "reactive oxygen species" (ROS) in a cyclic reaction between this substance and its reduction product, Dialuric Acid. The cytotoxic action of alloxan is initiated by free radicals formed in this redox reaction. Autoxidation of Dialuric Acid generates superoxide radicals (O(2)(*-)) and hydrogen peroxide (H(2)O(2)), and finally hydroxyl radicals ((*)OH). Thus, while superoxide dismutase (SOD) only reduced the toxicity, catalase, in particular in the presence of SOD, provided complete protection of insulin-producing cells against the cytotoxic action of alloxan and Dialuric Acid due to H(2)O(2) destruction and the prevention of hydroxyl radical ((*)OH) formation, indicating that it is the hydroxyl radical ((*)OH) which is the ROS ultimately responsible for cell death. After selective accumulation in pancreatic beta cells, which are weakly protected against oxidative stress, the cytotoxic glucose analogue alloxan destroys these insulin-producing cells and causes a state of insulin-dependent diabetes mellitus through ROS-mediated toxicity in rodents and in other animal species, which express this glucose transporter isoform in their beta cells.

Agung Endro Nugroho - One of the best experts on this subject based on the ideXlab platform.

  • review animal models of diabetes mellitus pathology and mechanism of some diabetogenics
    Biodiversitas, 2006
    Co-Authors: Agung Endro Nugroho
    Abstract:

    Animal models of diabetes mellitus were made and used in laboratorium according to the pathology of diabetic patient and its complications. Animal models of diabetes mellitus were designed by two methods: induced method such as pancreatectomy, chemicals (diabetogenic), viruses, and spontaneous method such BB (bio breeding) rats and NOD (non-obese diabetic) mice. The techniques of animal models of diabetes mellitus frequently used in the research were usage of diabetogenic such as alloxan and streptozotocin. Alloxan and its reduction metabolite (Dialuric Acid) establish a redox cycle and form superoxide radicals, and they undergo dismutation to hydrogen peroxide. By Fenton reaction, the formation of reactive hydroxyl radicals was stimulated. These radicals with high concentration of cytosolic calcium cause rapid destruction of I² cells. Besides, streptozotocin enters the I² cell through a glucose transporter (GLUT2), and stimulates superoxide radicals, hydrogen peroxide and hydroxyl radicals which in turn causes rapid destruction of I² cells. Streptozotocin also releases toxic amounts of nitric oxide that inhibits aconitase activity and contributes in DNA damage.© 2006 Jurusan Biologi FMIPA UNS SurakartaKey words: animal models, diabetes mellitus, alloxan, streptozotocin.

  • review hewan percobaan diabetes mellitus patologi dan mekanisme aksi diabetogenik animal models of diabetes mellitus pathology and mechanism of some diabetogenics
    2006
    Co-Authors: Agung Endro Nugroho
    Abstract:

    Animal models of diabetes mellitus were made and used in laboratorium according to the pathology of diabetic patient and its complications. Animal models of diabetes mellitus were designed by two methods: induced method such as pancreatectomy, chemicals (diabetogenic), viruses, and spontaneous method such BB (bio breeding) rats and NOD (non-obese diabetic) mice. The techniques of animal models of diabetes mellitus frequently used in the research were usage of diabetogenic such as alloxan and streptozotocin. Alloxan and its reduction metabolite (Dialuric Acid) establish a redox cycle and form superoxide radicals, and they undergo dismutation to hydrogen peroxide. By Fenton reaction, the formation of reactive hydroxyl radicals was stimulated. These radicals with high concentration of cytosolic calcium cause rapid destruction of β cells. Besides, streptozotocin enters the β cell through a glucose transporter (GLUT2), and stimulates superoxide radicals, hydrogen peroxide and hydroxyl radicals which in turn causes rapid destruction of β cells. Streptozotocin also releases toxic amounts of nitric oxide that inhibits aconitase activity and contributes in DNA damage. . © 2006 Jurusan Biologi FMIPA UNS Surakarta

  • Review: Animal Models of Diabetes Mellitus: Pathology and Mechanism of Some Diabetogenics
    MBI & UNS Solo, 2006
    Co-Authors: Agung Endro Nugroho
    Abstract:

    Animal models of diabetes mellitus were made and used in laboratorium according to the pathology of diabetic patient and its complications. Animal models of diabetes mellitus were designed by two methods: induced method such as pancreatectomy, chemicals (diabetogenic), viruses, and spontaneous method such BB (bio breeding) rats and NOD (non-obese diabetic) mice.The techniques of animal models of diabetes mellitus frequently used in the research were usage of diabetogenic such as alloxan and streptozotocin. Alloxan and its reduction metabolite (Dialuric Acid) establish a redox cycle and form superoxide radicals, and they undergo dismutation to hydrogen peroxide. By Fenton reaction, the formation of reactive hydroxyl radicals was stimulated. These radicals with high concentration of cytosolic calcium cause rapid destruction of β cells. Besides, streptozotocin enters the β cell through a glucose transporter (GLUT2), and stimulates superoxide radicals, hydrogen peroxide and hydroxyl radicals which in turn causes rapid destruction of β cells. Streptozotocin also releases toxic amounts of nitric oxide that inhibits aconitase activity and contributes in DNA damage

Matthias Elsner - One of the best experts on this subject based on the ideXlab platform.

  • relative importance of cellular uptake and reactive oxygen species for the toxicity of alloxan and Dialuric Acid to insulin producing cells
    Free Radical Biology and Medicine, 2006
    Co-Authors: Matthias Elsner, Ewa Gurgulconvey, S. Lenzen
    Abstract:

    The diabetogenic agent alloxan is selectively accumulated in insulin-producing cells through uptake via the GLUT2 glucose transporter in the plasma membrane. In the presence of intracellular thiols, especially glutathione, alloxan generates "reactive oxygen species" (ROS) in a cyclic reaction between this substance and its reduction product, Dialuric Acid. The cytotoxic action of alloxan is initiated by free radicals formed in this redox reaction. Autoxidation of Dialuric Acid generates superoxide radicals (O(2)(*-)) and hydrogen peroxide (H(2)O(2)), and finally hydroxyl radicals ((*)OH). Thus, while superoxide dismutase (SOD) only reduced the toxicity, catalase, in particular in the presence of SOD, provided complete protection of insulin-producing cells against the cytotoxic action of alloxan and Dialuric Acid due to H(2)O(2) destruction and the prevention of hydroxyl radical ((*)OH) formation, indicating that it is the hydroxyl radical ((*)OH) which is the ROS ultimately responsible for cell death. After selective accumulation in pancreatic beta cells, which are weakly protected against oxidative stress, the cytotoxic glucose analogue alloxan destroys these insulin-producing cells and causes a state of insulin-dependent diabetes mellitus through ROS-mediated toxicity in rodents and in other animal species, which express this glucose transporter isoform in their beta cells.

Bednarek Paweł - One of the best experts on this subject based on the ideXlab platform.

  • Mechanistic aspects of alloxan diabetogenic activity: a key role of keto-enol inversion of Dialuric Acid on ionization
    2007
    Co-Authors: Czerwiñska Małgorzata, Sikora Adam, Szajerski Piotr, Adamus Jan, Marcinek Andrzej, Gębicki Jerzy, Bednarek Paweł
    Abstract:

    The inversion of the keto-enol stability order of Dialuric Acid on ionization was calculated and verified experimentally. The radical cations in both forms were characterized. The spectrum of the keto form was observed upon direct ionization of Dialuric Acid under matrix conditions, whereas the enol form was formed upon a sequential electron-proton-proton attachment to alloxan under Acidic aqueous condition. Facilitation of the one-electron oxidation of Dialuric Acid upon its enolization can result in a more effective formation of superoxide radical anion in the process of its auto-oxidation. This process is discussed in reference to the alloxan diabetogenic action. Both neutral keto and enol forms are energetically close, and under favorable conditions, the auto-oxidation of Dialuric Acid could involve participation of the enol form

Paweł Bednarek - One of the best experts on this subject based on the ideXlab platform.

  • which should be cited to refer to this work. Mechanistic Aspects of Alloxan Diabetogenic Activity: A Key Role of Keto-Enol Inversion of Dialuric Acid on Ionization
    2014
    Co-Authors: Małgorzata Czerwiñska, Adam Sikora, Piotr Szajerski, Jan Adamus, Andrzej Marcinek, Paweł Bednarek
    Abstract:

    The inversion of the keto-enol stability order of Dialuric Acid on ionization was calculated and verified experimentally. The radical cations in both forms were characterized. The spectrum of the keto form was observed upon direct ionization of Dialuric Acid under matrix conditions, whereas the enol form was formed upon a sequential electron-proton-proton attachment to alloxan under Acidic aqueous condition. Facilitation of the one-electron oxidation of Dialuric Acid upon its enolization can result in a more effective formation of superoxide radical anion in the process of its auto-oxidation. This process is discussed in reference to the alloxan diabetogenic action. Both neutral keto and enol forms are energetically close, and under favorable conditions, the auto-oxidation of Dialuric Acid could involve participation of the enol form. 1