Journal
TRENDS IN PHARMACOLOGICAL SCIENCES
Volume 38, Issue 7, Pages 649-665Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2017.04.004
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Funding
- National Institutes of Health (NIH) Medical Scientist Training Program [T32 GM-007205]
- NIH National Research Service Award (NRSA) [F30 DK-104596]
- NIH [R01 DK-40936, P30 DK-045735]
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Although ample evidence links hepatic lipid accumulation with hepatic insulin resistance, the mechanistic basis of this association is incompletely understood and controversial. Diacylglycerols (DAGs) and ceramides have emerged as the two best-studied putative mediators of lipid-induced hepatic insulin resistance. Both lipids were first associated with insulin resistance in skeletal muscle and were subsequently hypothesized to mediate insulin resistance in the liver. However, the putative roles for DAGs and ceramides in hepatic insulin resistance have proved more complex than originally imagined, with various genetic and pharmacologic manipulations yielding a vast and occasionally contradictory trove of data to sort. In this review we examine the state of this field, turning a critical eye toward both DAGs and ceramides as putative mediators of lipid-induced hepatic insulin resistance.
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