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Treatment with a Catalytic Superoxide Dismutase (SOD) Mimetic Improves Liver Steatosis, Insulin Sensitivity, and Inflammation in Obesity-Induced Type 2 Diabetes

Coudriet, Gina and Delmastro-Greenwood, Meghan and Previte, Dana and Marré, Meghan and O’Connor, Erin and Novak, Elizabeth and Vincent, Garret and Mollen, Kevin and Lee, Sojin and Dong, H. and Piganelli, Jon (2017) Treatment with a Catalytic Superoxide Dismutase (SOD) Mimetic Improves Liver Steatosis, Insulin Sensitivity, and Inflammation in Obesity-Induced Type 2 Diabetes. Antioxidants, 6 (4). ISSN 2076-3921

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Oxidative stress and persistent inflammation are exaggerated through chronic over-nutrition and a sedentary lifestyle, resulting in insulin resistance. In type 2 diabetes (T2D), impaired insulin signaling leads to hyperglycemia and long-term complications, including metabolic liver dysfunction, resulting in non-alcoholic fatty liver disease (NAFLD). The manganese metalloporphyrin superoxide dismustase (SOD) mimetic, manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnP), is an oxidoreductase known to scavenge reactive oxygen species (ROS) and decrease pro-inflammatory cytokine production, by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. We hypothesized that targeting oxidative stress-induced inflammation with MnP would assuage liver complications and enhance insulin sensitivity and glucose tolerance in a high-fat diet (HFD)-induced mouse model of T2D. During 12 weeks of feeding, we saw significant improvements in weight, hepatic steatosis, and biomarkers of liver dysfunction with redox modulation by MnP treatment in HFD-fed mice. Additionally, MnP treatment improved insulin sensitivity and glucose tolerance, while reducing serum insulin and leptin levels. We attribute these effects to redox modulation and inhibition of hepatic NF-κB activation, resulting in diminished ROS and pro-inflammatory cytokine production. This study highlights the importance of controlling oxidative stress and secondary inflammation in obesity-mediated insulin resistance and T2D. Our data confirm the role of NF-κB-mediated inflammation in the development of T2D, and demonstrate the efficacy of MnP in preventing the progression to disease by specifically improving liver pathology and hepatic insulin resistance in obesity


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Coudriet, Gina
Delmastro-Greenwood, Meghan
Previte, Danadmp51@pitt.edudmp51
Marré, Meghan
O’Connor, Erin
Novak, Elizabethean17@pitt.eduean17
Vincent, Garret
Mollen, Kevinkpm23@pitt.edukpm23
Lee, Sojinsol24@pitt.edusol24
Dong, H.dongh@pitt.edudongh
Piganelli, Jonjdp51@pitt.edujdp51
Date: 11 January 2017
Date Type: Publication
Journal or Publication Title: Antioxidants
Volume: 6
Number: 4
Publisher: MDPI AG
DOI or Unique Handle: 10.3390/antiox6040085
Schools and Programs: School of Medicine > Surgery
Refereed: Yes
Uncontrolled Keywords: SOD mimetic, metalloporphyrin, inflammation, type 2 diabetes, NAFLD, obesity, insulin resistance
ISSN: 2076-3921
Official URL:
Funders: NIH, American Diabetes Association
Article Type: Research Article
Date Deposited: 11 Jan 2021 23:20
Last Modified: 11 Jan 2021 23:20


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