Response to Comment on: Reyna et al. (2008) Elevated Toll-Like Receptor 4 Expression and Signaling in Muscle From Insulin-Resistant Subjects. Diabetes 57:2595–2602
- Sara M. Reyna1,2,
- Sangeeta Ghosh1,2,
- Ralph A. DeFronzo1,2,
- Christopher P. Jenkinson1,2 and
- Nicolas Musi1,2
- 1Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas; and
- 2Texas Diabetes Institute, San Antonio, Texas.
- Corresponding author: Nicolas Musi, nicolas.musi{at}uhs-sa.com.
We thank Shapiro et al. (1) for their interest in our study (2) and their comment about the role of low-grade endotoxemia in the pathogenesis of insulin resistance in type 2 diabetic subjects. The notion that elevated levels of lipopolysaccharide (LPS) in the circulation derived from a gastrointestinal source could be responsible for the inflammatory state present in insulin-resistant subjects (3,4) is provocative and merits further investigation. Although caution is warranted when extrapolating from a small number of studies (3,4), in the future it would be useful to measure circulating LPS levels in insulin-resistant subjects and determine whether a correlation exists between the plasma LPS concentration and toll-like receptor (TLR)4 expression/signaling in tissue.
As pointed out by Shapiro et al. (1), there is some evidence (obtained mostly in inflammatory cells) indicating that pre-exposure to LPS decreases the response to subsequent …
