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Effect of Inflammation on Ketoisocaproic Acid Induced Insulin Resistance In Skeletal Muscle Cells

Effect of Inflammation on Ketoisocaproic Acid Induced Insulin Resistance In Skeletal Muscle Cells

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Title: Effect of Inflammation on Ketoisocaproic Acid Induced Insulin Resistance In Skeletal Muscle Cells
Author: Mann, Gagandeep Singh
Abstract: Branched-chain amino acids (BCAAs) have displayed metabolic benefits, and play a role in muscle protein synthesis. However, elevated levels of BCAAs and their metabolites have been linked to the pathogenesis of insulin resistance and type 2 diabetes mellitus. It has been demonstrated in my lab that -ketoisocaproic acid (KIC), a metabolite of leucine, inhibited insulin-stimulated glucose uptake, but is converted back to leucine in order to do so. Inflammation, a feature of insulin resistance may modulate the effects of amino acids and their metabolites on insulin action. Thus, I analyzed whether or not there was an additive effect of KIC and inflammation on insulin-stimulated glucose transport in L6 myotubes. Results emphasize previous findings, that even in the presence of inflammation, KIC is converted back to leucine to inhibit insulin-stimulated glucose uptake, suggesting that interventions altering BCAA pathway flux may help in the management/prevention of insulin resistance.
Subject: Cellular biology
Keywords: Insulin resistance
skeletal muscle
glucose transport
leucine
KIC
mTORC1
inflammation
glycogen synthesis
insulin signaling
diabetes
siRNA
BCAAs
branched-chain amino acids.
Type: Electronic Thesis or Dissertation
Rights: Author owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
URI: http://hdl.handle.net/10315/35889
Supervisor: Adegoke, Olasunkanmi A. J.
Degree: MSc - Master of Science
Program: Kinesiology & Health Science
Exam date: 2018-11-21
Publish on: 2019-03-05

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