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Role of adipocyte-derived factors in enhancing insulin signaling in skeletal muscle and white adipose tissue of mice lacking Acyl CoA:diacylglycerol acyltransferase 1.
- Source :
- Diabetes; Jun2004, Vol. 53 Issue 6, p1445-1451, 7p, 9 Graphs
- Publication Year :
- 2004
-
Abstract
- Mice that lack acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in mammalian triglyceride synthesis, have decreased adiposity and increased insulin sensitivity. Here we show that insulin-stimulated glucose transport is increased in the skeletal muscle and white adipose tissue (WAT) of chow-fed DGAT1-deficient mice. This increase in glucose transport correlated with enhanced insulin-stimulated activities of phosphatidylinositol 3-kinase, protein kinase B (or Akt), and protein kinase Clambda (PKC-lambda), three key molecules in the insulin-signaling pathway, and was associated with decreased levels of serine-phosphorylated insulin receptor 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-fat diet. Interestingly, the increased PKC-lambda activity and decreased serine phosphorylation of IRS-1 were observed in chow-fed wild-type mice transplanted with DGAT1-deficient WAT, consistent with our previous finding that transplantation of DGAT1-deficient WAT enhances glucose disposal in wild-type recipient mice. Our findings demonstrate that DGAT1 deficiency enhances insulin signaling in the skeletal muscle and WAT, in part through altered expression of adipocyte-derived factors that modulate insulin signaling in peripheral tissues. [ABSTRACT FROM AUTHOR]
- Subjects :
- ACYLTRANSFERASES
COENZYMES
INSULIN
GLUCOSE
ADIPOSE tissues
MUSCLES
ADIPOSE tissue transplantation
PROTEIN metabolism
GLUCOSE metabolism
SERINE metabolism
ANIMAL experimentation
CARRIER proteins
CELLULAR signal transduction
DOSE-effect relationship in pharmacology
FAT cells
FAT content of food
ISOENZYMES
MICE
PHOSPHOPROTEINS
PHOSPHORYLATION
PHOSPHOTRANSFERASES
RESEARCH funding
TRANSFERASES
SKELETAL muscle
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 53
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 13260877
- Full Text :
- https://doi.org/10.2337/diabetes.53.6.1445