Abstract
The anti-diabetic effect of cytogenin was examined using streptozotocin-induced diabetes in mice. Cytogenin suppressed not only the increase of plasma glucose level but also the body weight reduction in diabetic mice. Histological examination of the pancreas taken from diabetic mice given cytogenin showed that cytogenin decreased the number of macrophages infiltrated into islet of pancreas. Further, cytogenin suppressed the nitric oxide generation by macrophages treated with lipopolysaccharide through decreasing of inducible nitric oxide synthase expression. Cytogenin suppressed interleukin-6 expression by macrophage treated with LPS, suggesting that the anti-diabetic activity of cytogenin might be partly attributed to the suppressive activity against nitric oxide generation.
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Kumagai H, Masuda T, Osono M, Hattori S, Naganawa H, Sawa T, Hamada M, Ishizuka M, Takeuchi T . Cytogenin, a novel antitumor substance. J Antibiot 43: 1505–1507 ( 1990)
Kumagai H, Masuda T, Ishizuka M, Takeuchi T . Antitumor activity of cytogenin. J Antibiot 48: 175–178 ( 1995)
Kumagai H, Osono M, Iijima M, Sakashita M, Ishizuka M, Takeuchi T . Action of cytogenin on lymphoid cells and their cytokine production. J Antibiot 48: 317–320 ( 1995)
Kumagai H, Masuda T, Sakashita M, Ishizuka M, Takeuchi T . Modulation of macrophage activity on tumor bearing mice by cytogenin. J Antibiot 48: 321–325 ( 1995)
Hirano S, Wakazono K, Agata N, Mase T, Yamamoto R, Matsufuji M, Sakata N, Iguchi H, Tone H, Ishizuka M, Takeuchi T, Abe C . Effects of cytogenin, a novel anti-arthritic agent, on type II collagen-induced arthritis in DBA/1J mice and adjuvant arthritis in Lewis rats. Int J Tissue React 16: 155–162 ( 1994)
Abe C, Hirano S, Wakazono K, Mase T, Yamamoto R, Matsufuji M, Sakata N, Agata N, Iguchi H, Ishizuka M, et al. Effects of cytogenin on spontaneous arthritis in MRL/1 mice and on pristane-induced arthritis (PIA) in DBA/1J mice. Int J Tissue React 17: 175–180 ( 1995)
Nakamura M, Nagafuchi S, Yamaguchi K, Takaki R . The role of thymic immunity and insulitis in the development of streptozocin-induced diabetes in mice. Diabetes 33: 894–900 ( 1984)
Keller R, Keist R . Abilities of activated macrophages to manifest tumoricidal activity and to generate reactive nitrogen intermediates: a comparative study in vitro and ex vivo. Biochem Biophys Res Commun 164: 968–973 ( 1989)
Roth SI, Conaway HH, Sanders LL, Casali RE, Boyd AE . Spontaneous diabetes mellitus in the New Zealand white rabbit: preliminary morphologic characterization. Lab Invest 42: 571–579 ( 1980)
Sadelain MW, Qin HY, Lauzon J, Singh B . Prevention of type I diabetes in NOD mice by adjuvant immunotherapy. 39: 583–589 ( 1990)
Darville MI, Eizirik DL . Regulation by cytokines of the inducible nitric oxide synthase promoter in insulin-producing cells. Diabetologia 41: 1101–1108 ( 1998)
Flodstrom M, Tyrberg B, Eizirik DL, Sandler S . Reduced sensitivity of inducible nitric oxide synthase-deficient mice to multiple low-dose streptozotocin-induced diabetes. Diabetes 48: 706–713 ( 1999)
Kato Y, Miura Y, Yamamoto N, Ozaki N, Oiso Y . Suppressive effects of a selective inducible nitric oxide synthase (iNOS) inhibitor on pancreatic beta-cell dysfunction. Diabetologia 46: 1228–1233 ( 2003)
Tuna M, Polat S, Erman T, Ildan F, Gocer AI, Tuna N, Tamer L, Kaya M, Cetinalp E . Effect of anti-rat interleukin-6 antibody after spinal cord injury in the rat: inducible nitric oxide synthase expression, sodium- and potassium-activated, magnesium-dependent adenosine-5′-triphosphatase and superoxide dismutase activation, and ultrastructural changes. J Neurosurg 95: 64–73 ( 2001)
Wadt KA, Larsen CM, Andersen HU, Nielsen K, Karlsen AE, Mandrup-Poulsen T . Ciliary neurotrophic factor potentiates the beta-cell inhibitory effect of IL-1beta in rat pancreatic islets associated with increased nitric oxide synthesis and increased expression of inducible nitric oxide synthase. Diabetes 47: 1602–1608 ( 1998)
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Kumagai, H., Wakazono, K., Agata, N. et al. Effect of Cytogenin, a Novel Immunomodulator, on Streptozotocin-induced Diabetes in Mice. J Antibiot 58, 202–205 (2005). https://doi.org/10.1038/ja.2005.24
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DOI: https://doi.org/10.1038/ja.2005.24