Dynamic PET Imaging Reveals Heterogeneity of Skeletal Muscle Insulin Resistance Article

Industry Collaboration International Collaboration

cited authors

  • Ng, Jason M., Bertoldo, Alessandra, Minhas, Davneet S., Helbling, Nicole L., Coen, Paul M., Price, Julie C., Cobelli, Claudio, Kelley, David E., Goodpaster, Bret H.

funding text

  • This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-60555-02), the University of Pittsburgh General Clinical Research Center (5MO1RR00056), and the Obesity and Nutrition Research Center (NIDDK P30-DK-46204).

abstract

  • Purpose: Skeletal muscle insulin resistance (IR) often precedes hyperglycemia and type 2 diabetes. However, variability exists within different skeletal muscle types and can be influenced by 3 primary steps of control: glucose delivery, transport, and phosphorylation. We performed dynamic positron emission tomography imaging studies to determine the extent to which heterogeneity in muscle type and control of insulin action contribute to IR. Methods: Thirteen volunteers from normal weight to obese underwent dynamic positron emission tomography imaging of [O-15]H2O, [C-11]3-O-methylglucose, and [F-18]fluorodeoxyglucose, measuring delivery, transport, and phosphorylation rates, respectively, in soleus and tibialis anteriormuscleduring a hyperinsulinemic-euglycemic clamp. Subjects were classified as insulin-sensitive (IS) or insulin-resistant (IR) based on the median systemic glucose infusion rate needed to maintain euglycemia. Results: In soleus, transport kinetic rates were significantly higher (P < .05) in IS (0.126 +/- 0.028 min(-1)) vs IR (0.051 +/- 0.008 min(-1)) subjects. These differences were not as evident in tibialis anterior. These differences were paralleled in overall insulin-stimulated tissue activity, higher in IS (0.017 +/- 0.001 mL.cm(3).min(-1)) vs IR (0.011 +/- 0.002 mL.cm(3).min(-1)) in soleus (P < .05), without significant differences in tibialis anterior. No significant differences were observed for either muscle in delivery or phosphorylation. Both muscle types displayed a control shift from an even distribution among the steps in IS to transport exerting greater control of systemic insulin sensitivity in IR. Conclusion: Lower glucose transport rates are the major feature underlying IR preceding type 2 diabetes, although substantial heterogeneity in insulin action across muscle types highlight the complexity of skeletal muscle IR.

authors

Publication Date

  • January 1, 2014

webpage

published in

category

start page

  • E102

end page

  • E106

volume

  • 99

issue

  • 1

WoS Citations

  • 8

WoS References

  • 18