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You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Additional advisors: Jeonga Kim, John D. Mountz, Alexander Pereboev, Selvarangan Ponnazhagan."). One record found.

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1. Jiang, Shaoning. Molecular mechanisms of hepatic insulin resistance following injury.

Degree: PhD, 2010, University of Alabama – Birmingham

Insulin resistance commonly occurs following injuries or critical illness independent of previous diabetic status. The development of insulin resistance and hyperglycemia is associated with increased mortality and morbidity in critically ill patients. However, the molecular mechanisms underlying the acute insulin resistance following injuries remain poorly understood. With an animal model of trauma and hemorrhage, we have previously demonstrated the rapid development of insulin resistance in liver, and a critical role of TNF? in hemorrhage-induced defects in insulin signaling following resuscitation. However, hepatic insulin signaling is impaired prior to a significant increase in plasma TNF?, suggesting the initial development of hemorrhage-induced hepatic insulin resistance may be TNF? independent. By inhibiting the activity of TNF? or reactive oxygen species (ROS), our current studies further demonstrated that elevated ROS is responsible for the initial development of hepatic insulin resistance following hemorrhage, while TNF? has a dominant role later, following resuscitation. The mechanisms by which ROS induces the rapid development of hepatic insulin resistance were next investigated. Both Inhibitory-?B kinases (IKK) and c-Jun Nterminal kinase (JNK) can be activated by ROS and inhibit insulin signaling, potentially by increasing serine phosphorylation of insulin receptor (IR) or insulin receptor substrates (IRSs). Activation of hepatic IKK and JNK was observed as early as 15 minutes after trauma and hemorrhage, which was concomitant with the rapid impairment of hepatic insulin signaling. The important roles of IKK and JNK in the early development of hemorrhage-induced insulin resistance were further demonstrated by direct inhibition of the IKKs (IKK? and ?) and JNK1 with adenovirus-mediated expression of dominant negative mutants of IKKs and JNK1 in liver. Using two approaches of Kupffer celldepletion, we further demonstrated that the early development of hemorrhage-induced hepatic insulin resistance and activation of IKK and JNK are Kupffer cell independent. Thus, acute activation of IKK and JNK likely occurs within hepatocytes where they directly interact with IR or IRS proteins and inhibit insulin signaling. In conclusion, our studies provide mechanistic insights into the acute onset of hepatic insulin resistance following injury. IKK and JNK are potential therapeutic targets for treating hyperglycemia in the Intensive Care Unit.

1 online resource (xii, 199 p.) :ill., digital, PDF file.

Joint Health Sciences

Acute insulin resistance, Injury, Liver, TNF?, Serine kinase, Kupffer cell

UNRESTRICTED

Advisors/Committee Members: Joseph L. Messina, Additional advisors: Jeonga Kim, John D. Mountz, Alexander Pereboev, Selvarangan Ponnazhagan..

Subjects/Keywords: Adenoviridae – metabolism<; br>; Adenoviridae Infections – metabolism<; br>; Diabetes Mellitus, Type 2 – physiopathology<; br>; Glucose – metabolism<; br>; I-kappa B Kinase – physiology <; br>; Insulin – metabolism<; br>; JNK Mitogen-Activated Protein Kinases – physiology <; br>; Liver

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Jiang, S. (2010). Molecular mechanisms of hepatic insulin resistance following injury. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1374

Chicago Manual of Style (16th Edition):

Jiang, Shaoning. “Molecular mechanisms of hepatic insulin resistance following injury.” 2010. Doctoral Dissertation, University of Alabama – Birmingham. Accessed October 20, 2019. http://contentdm.mhsl.uab.edu/u?/etd,1374.

MLA Handbook (7th Edition):

Jiang, Shaoning. “Molecular mechanisms of hepatic insulin resistance following injury.” 2010. Web. 20 Oct 2019.

Vancouver:

Jiang S. Molecular mechanisms of hepatic insulin resistance following injury. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2010. [cited 2019 Oct 20]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1374.

Council of Science Editors:

Jiang S. Molecular mechanisms of hepatic insulin resistance following injury. [Doctoral Dissertation]. University of Alabama – Birmingham; 2010. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1374

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