Review article
Free radicals and diabetes

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Abstract

The role of active oxygene species in diabetes is discussed in this review. Type I diabetes is caused by destruction of the pancreatic beta cells responsible for producing insulin. In humans, the diabetogenic process appears to be caused by immune destruction of the beta cells; part of this process is apparently mediated by white cell production of active oxygen species. Diabetes can be produced in animals by the drugs alloxan and streptozotocin; the mechanism of action of these two drugs is different, but both result in the production of active oxygen species. Scavengers of oxygen radicals are effective in preventing diabetes in these animal models. Not only are oxygen radicals involved in the cause of diabetes, they also appear to play a role in some of the complications seen in long-term treatment of diabetes. Changes in antioxidants in the diabetic state and their consequences are discussed.

References (110)

  • R.E. Heikkila et al.

    The prevention of alloxan induced diabetes by amygdalin

    Life Sci.

    (1980)
  • W.K. Meckstroth et al.

    Reactivity of the hydroxyl radical with amygdalin in aqueous solution

    Biochem. Pharmacol.

    (1980)
  • W.B. Cowden et al.

    Protection against alloxan-induced diabetes in mice by the free radical scavenger butylated hydroxyanisole

    Biochem. Pharmacol.

    (1985)
  • K. Grankvist et al.

    Opposite effects of two metal chelators on alloxan-induced diabetes in mice

    Life Sci.

    (1983)
  • L.M. Srivastava et al.

    Diabetogenic action of streptozotocin

    Trends Pharmacol. Sci.

    (1982)
  • B.C.F. Chu et al.

    Increased urinary excreation of nucleic acid and nicotinamide derivatives by rats after treatment with alkylating agents

    Chem. Biol. Interact.

    (1975)
  • B.C.F. Chu et al.

    Increased urinary excretion of pyrimidine and nicotinamide derivatives in rats treated with methyl methanesulphonate

    Chem. Biol. Interact.

    (1974)
  • M. Hinz et al.

    Significance of streptozotocin induced niotinamide- adenine-dinucleotide (NAD) degradation in mouse tissue islets

    FEBS Lett.

    (1973)
  • K. Arai et al.

    Increase in the glucosylated form of erythrocyte Cu-Zn-superoxide dismutase in diabetes and close association of the nonenzymatic glucosylation with the enzyme activity

    Biochim. Biophys. Acta

    (1987)
  • S.L. Marklund et al.

    Plasma EC-superoxide dismutasea activity in insulin-dependent diabetic children

    Clin. Chim. Acta

    (1984)
  • M. Bitar et al.

    Heme and hemoproteins in streptozotocin-diabetic female rats

    Biochem. Pharmacol.

    (1983)
  • P. Zimmet

    Epidemiology of diabetes mellitus

  • M.A. Charles et al.

    Immune islet killing mechanisms with insulin-dependent diabtes: in vitro expression of cellular and antibody-mediated islet cell cytotoxicity in humans

    J. Immunol.

    (1983)
  • P. Pozilli et al.

    Monoclonal antibodies defined abnormalities of T-lymphocytes in type I (insulin-dependent) diabetes

    Diabetes

    (1983)
  • S. Kataoka et al.

    Immunologic aspects of the nonobese diabetic (NOD) mouse: abnormalities of cellular immunity

    Diabetes

    (1983)
  • M. DeBray-Sachs et al.

    Anti-islet immunity and thymic dysfunction in the mutant diabetic C57BL/KsJ db/db mouse

    Diabetes

    (1983)
  • A.A. Like et al.

    Spontaneous diabetes mellitus: reversal and prevention in the BB/W rat with antiserum to rat lymphocytes

    Science

    (1979)
  • S.-G. Paik et al.

    Diabetes susceptibility of Balb/cBOM mice treated with steptozotocin; inhibition of lethal irradiation and restoration of splenic lymphocytes

    Diabetes

    (1982)
  • S.-G. Paik et al.

    Insulin dependent diabetes mellitus induced by subdiabetogenic doses of strptozotocin: obligatory role of cell mediated autoimmune process

  • I.N. Nomikos et al.

    Combined treatment with nicotinamide and desferrioxamine prevents islet allograft destruction in NOD mice

    Diabetes

    (1986)
  • S.E. Gandy et al.

    Superoxide dismutase in human islets of Langerhans

    N. Engl. J. Med.

    (1981)
  • R. Crouch et al.

    Localization of SOD in the cornea and pancreas by light and electron microscopy

  • R.K. Crouch et al.

    The inhibition of islet superoxide dismutase by diabetogenic drugs

    Diabetes

    (1981)
  • K. Grankvist et al.

    CuZn-superoxide dismutase, MN superoxide dismutase, catalae, and glutathione peroxidase in pancreatic islets and other tissues in the mouse

    Biochem.J.

    (1981)
  • W.J. Malaisse et al.

    Determinants of the selective toxicity of alloxan to the pancreatic β cell

  • K. Asayama et al.

    Effect of vitamin E deficiency and selenium deficiency on insulin secretory reserve and free radical scavenging systems in islets: decrease of islet manganosuperoxide dismutase

    J. Lab. Clin. Med.

    (1986)
  • C.C. Rerup

    Drugs producing diabetes through damage of the insulin secreting cells

    Pharmacol. Rev.

    (1970)
  • W.E. Dulin et al.

    Experimentla and spontaneous diabetes in animals

  • D.W. Deamer et al.

    The alloxan-dialuric acid cycle and the generation of hydrogen peroxide

    Phys. Chem. Phys.

    (1971)
  • K. Grankvist

    Alloxan-induced luminol luminescence as a tool for investigating mechanisms of radical-mediated diabetogenicity

    Biochem. J.

    (1981)
  • L.J. Fisher et al.

    Dimethylurea, a radical scavenger that protects pancreatic islets from the effects of alloxan and dihydroxyfumarate exposure

    Life Sci.

    (1980)
  • K. Grankvist et al.

    Superoxide dismutase, catalase, and scavengers of hydroxyl radical protect against toxic action of alloxan on pancreatic islet cells in vitro

    Biochem. J.

    (1979)
  • L.J. Fischer et al.

    Inhibition of alloxan action in isolated pancreatic islets by superoxide dismutase, catalase, and a metal chelator

    Diabetes

    (1980)
  • K. Asayama et al.

    Chemiluminescence as an index of drug-induced free radical production in pancreatic islets

    Diabetes

    (1984)
  • K. Asayama et al.

    Alloxan-induced free radical production in isolated cells. Selective effect on islet cells

    Diabetes

    (1984)
  • H. Okamoto et al.

    Protection by superoxide dismutase, catalase, and poly(ADP-ribose) synthetase inhibitors against alloxan-and streptozotocin-induced islet DNA strand breaks and against proinsulin synthesis.

  • A. Scheynius et al.

    On the mechanism of glucose protection against alloxan toxicity

    Diabetologia

    (1971)
  • A.L. Sagone et al.

    Glucose: a free radical scavenger in biological systems

    J. Lab. Clin. Med.

    (1983)
  • J. Tibaldi et al.

    Protection against alloxan-induced diabetes by various urea derivatives: relatioship between protective effects and reactivity with the hydroxyl radical

    J. Pharmacol. Exp. Ther.

    (1979)
  • A.E. Slonim et al.

    Modification of chemically induced diabetes in rats by vitamin E: supplementation minimizes and depletion enhances development of diabetes

    J. Clin. Invest.

    (1983)
  • Cited by (0)

    Larry W. Oberley received his undergraduate education in physics at Northwestern University. He received the M.S. and Ph.S. degrees in physics from the University of Iowa. His Ph.D. dissertation was on the Mossbauer effect of biological compounds. This research sparked his interest in biology and biochemistry which has been his focus since. In 1975, Dr. Oberley joined the Radiation Research Laboratory at the University of Iowa shere he has remained. In 1985, he was appointed Professor of Radiology. Dr. Oberley's main research interest is the role of oxygen free radicals and antioxidant enzymes in cancer; in recent year, this research has gravitated toward the molecular biology of the antioxidant enzymes in tumor cells. Dr. Oberley has edited three volumes entitled Superoxide Dismutase for CRC Press.

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