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Tetrahydroindenoindole inhibits the progression of diabetes in mice.

Publication ,  Journal Article
Shertzer, HG; Schneider, SN; Kendig, EL; Clegg, DJ; D'Alessio, DA; Johansson, E; Genter, MB
Published in: Chem Biol Interact
January 15, 2009

Diabetes is characterized by elevated fasting blood glucose (FBG) resulting from improper insulin regulation and/or insulin resistance. Herein we used female C57BL/6J mouse models for type 1 diabetes (streptozotocin [STZ] treatment) and type 2 diabetes (high-fat diet) to examine the ability of 4b,5,9b,10-tetrahydroindeno[1,2-b]indole (THII) to intervene in the progression of diabetes. THII (100 microM in drinking water) significantly diminished and partially reversed the increase in FBG levels produced by STZ. After 10 weeks on a high-fat diet, mice had normal FBG levels, but exhibited fasting hyperinsulemia and loss of glucose tolerance. THII significantly diminished these changes in glucose and insulin. In isolated liver mitochondria, THII inhibited succinate-dependent H(2)O(2) production, while in white adipose tissue, THII inhibited NADPH oxidase-mediated H(2)O(2) production and lipid peroxidation. Without intervention, such oxidative processes might otherwise promote diabetogenesis via inflammatory pathways. THII also increased O(2) consumption and lowered respiratory quotient (CO(2) produced/O(2) consumed) in vivo, indicating a greater utilization of fat for metabolic fuel. Increased metabolic utilization of fat correlated with a decrease in the rate of body weight gain in THII-treated mice fed the high-fat diet. We conclude that THII may retard the progression of diabetes via multiple pathways, including the inhibition of oxidative and inflammatory pathways.

Duke Scholars

Published In

Chem Biol Interact

DOI

EISSN

1872-7786

Publication Date

January 15, 2009

Volume

177

Issue

1

Start / End Page

71 / 80

Location

Ireland

Related Subject Headings

  • Toxicology
  • Streptozocin
  • Oxidative Stress
  • NADPH Oxidases
  • Models, Biological
  • Mitochondria, Liver
  • Mice
  • Insulin
  • Indoles
  • Hyperglycemia
 

Citation

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Shertzer, H. G., Schneider, S. N., Kendig, E. L., Clegg, D. J., D’Alessio, D. A., Johansson, E., & Genter, M. B. (2009). Tetrahydroindenoindole inhibits the progression of diabetes in mice. Chem Biol Interact, 177(1), 71–80. https://doi.org/10.1016/j.cbi.2008.09.001
Shertzer, Howard G., Scott N. Schneider, Eric L. Kendig, Deborah J. Clegg, David A. D’Alessio, Elisabet Johansson, and Mary Beth Genter. “Tetrahydroindenoindole inhibits the progression of diabetes in mice.Chem Biol Interact 177, no. 1 (January 15, 2009): 71–80. https://doi.org/10.1016/j.cbi.2008.09.001.
Shertzer HG, Schneider SN, Kendig EL, Clegg DJ, D’Alessio DA, Johansson E, et al. Tetrahydroindenoindole inhibits the progression of diabetes in mice. Chem Biol Interact. 2009 Jan 15;177(1):71–80.
Shertzer, Howard G., et al. “Tetrahydroindenoindole inhibits the progression of diabetes in mice.Chem Biol Interact, vol. 177, no. 1, Jan. 2009, pp. 71–80. Pubmed, doi:10.1016/j.cbi.2008.09.001.
Shertzer HG, Schneider SN, Kendig EL, Clegg DJ, D’Alessio DA, Johansson E, Genter MB. Tetrahydroindenoindole inhibits the progression of diabetes in mice. Chem Biol Interact. 2009 Jan 15;177(1):71–80.
Journal cover image

Published In

Chem Biol Interact

DOI

EISSN

1872-7786

Publication Date

January 15, 2009

Volume

177

Issue

1

Start / End Page

71 / 80

Location

Ireland

Related Subject Headings

  • Toxicology
  • Streptozocin
  • Oxidative Stress
  • NADPH Oxidases
  • Models, Biological
  • Mitochondria, Liver
  • Mice
  • Insulin
  • Indoles
  • Hyperglycemia