Send to

Choose Destination
Diabetes. 2010 Jan;59(1):80-8. doi: 10.2337/db09-0988. Epub 2009 Oct 15.

Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content.

Author information

Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.



We tested the primary hypotheses that sphingolipid and diacylglycerol (DAG) content is higher within insulin-resistant muscle and that the association between intramyocellular triglycerides (IMTG) and insulin resistance is muscle fiber type specific.


A nested case-control analysis was conducted in 22 obese (BMI >30 kg/m(2)) women who were classified as insulin-resistant (IR; n = 12) or insulin-sensitive (IS; n = 10), determined by hyperinsulinemic-euglycemic clamp (>30% greater in IS compared with IR, P < 0.01). Sphingolipid and DAG content was determined by high-performance liquid chromatography-tandem mass spectrometry. Fiber type-specific IMTG content was histologically determined. Gene expression was determined by quantitative PCR.


Total (555 +/- 53 vs. 293 +/- 54 pmol/mg protein, P = 0.004), saturated (361 +/- 29 vs. 179 +/- 34 pmol/mg protein, P = 0.001), and unsaturated (198 +/- 29 vs. 114 +/- 21 pmol/mg protein, P = 0.034) ceramides were higher in IR compared with IS. DAG concentrations, however, were similar. IMTG content within type I myocytes, but not type II myocytes, was higher in IR compared with IS subjects (P = 0.005). Insulin sensitivity was negatively correlated with IMTG within type I myocytes (R = -0.51, P = 0.026), but not with IMTG within type II myocytes. The proportion of type I myocytes was lower (41 vs. 59%, P < 0.01) in IR subjects. Several genes involved in lipid droplet and fatty acid metabolism were differentially expressed in IR compared with IS subjects.


Human skeletal muscle insulin resistance is related to greater IMTG content in type I but not type II myocytes, to greater ceramide content, and to alterations in gene expression associated with lipid metabolism.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center