The role of adipocyte-derived factors in enhancing insulin signaling in skeletal muscle and white adipose tissue of mice lacking acyl coenzyme A:diacylglycerol acyltransferase 1. Diabetes

Mice that lack acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in mammalian triglyceride syn-thesis, have decreased adiposity and increased insulin sensitivity. Here we show that insulin-stimulated glu-cose transport is increased in the skeletal muscle and white adipose tissue (WAT) of chow-fed DGAT1-defi-cient mice. This increase in glucose transport correlated with enhanced insulin-stimulated activities of phospha-tidylinositol 3-kinase, protein kinase B (or Akt), and protein kinase C (PKC-), three key molecules in the insulin-signaling pathway, and was associated with de-creased levels of serine-phosphorylated insulin recep-tor substrate 1 (IRS-1), a molecule implicated in insulin resistance. Similar findings in insulin signaling were also observed in DGAT1-deficient mice fed a high-fa