TY - JOUR
T1 - Intramyocellular lipids
T2 - Maker vs. marker of insulin resistance
AU - Guo, Zeng Kui
N1 - Funding Information:
The work is supported by NIH research Project R01 Grant DK 60013 and ADA Research Award 7-05-RA-48. The author thanks Dr. Michael D. Jensen for stimulating discussions. The technical assistance provided by Lianzhen Zhou (Ph.Lic.) is appreciated that is critical for obtaining the data as mentioned herein.
PY - 2008
Y1 - 2008
N2 - Intramyocellular triglyceride (imcTG) content in skeletal muscle is abnormally high in lipid oversupply models in obesity, type 2 diabetes (T2D) and other metabolically diseased conditions. The imcTG abnormality was also found to be significantly correlated with muscle insulin resistance (MIR). As skeletal muscle is the main site for insulin-mediated glucose utilization, the research on this topic has been active since. However, to date the pathways responsible for the imcTG excess and the mechanisms underlying the imcTG-MIR correlation have not been identified. A current view is focused on a backward mechanism that fatty acid oxidation by muscle is impaired causing imcTG to accumulate and, therefore, an enlarged imcTG pool is merely a marker of MIR. However, based on kinetic studies, it is more likely that imcTG is a source of MIR. On one hand, an enlarged and fast turning over imcTG pool interferes with insulin signaling by producing excess amounts of signaling molecules that activate PKC pathways. On the other hand, it may promote mitochondrial β-oxidation that suppresses glucose metabolism via substrate competition. Therefore, it is hypothesized that imcTG is a source of MIR.
AB - Intramyocellular triglyceride (imcTG) content in skeletal muscle is abnormally high in lipid oversupply models in obesity, type 2 diabetes (T2D) and other metabolically diseased conditions. The imcTG abnormality was also found to be significantly correlated with muscle insulin resistance (MIR). As skeletal muscle is the main site for insulin-mediated glucose utilization, the research on this topic has been active since. However, to date the pathways responsible for the imcTG excess and the mechanisms underlying the imcTG-MIR correlation have not been identified. A current view is focused on a backward mechanism that fatty acid oxidation by muscle is impaired causing imcTG to accumulate and, therefore, an enlarged imcTG pool is merely a marker of MIR. However, based on kinetic studies, it is more likely that imcTG is a source of MIR. On one hand, an enlarged and fast turning over imcTG pool interferes with insulin signaling by producing excess amounts of signaling molecules that activate PKC pathways. On the other hand, it may promote mitochondrial β-oxidation that suppresses glucose metabolism via substrate competition. Therefore, it is hypothesized that imcTG is a source of MIR.
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U2 - 10.1016/j.mehy.2007.03.044
DO - 10.1016/j.mehy.2007.03.044
M3 - Article
C2 - 17766054
AN - SCOPUS:38849194111
SN - 0306-9877
VL - 70
SP - 625
EP - 629
JO - Medical Hypotheses
JF - Medical Hypotheses
IS - 3
ER -