Display options
Cite
Vaitheesvaran B, Chueh FY, Xu J, et al. Advantages of dynamic "closed loop" stable isotope flux phenotyping over static "open loop" clamps in detecting silent genetic and dietary phenotypes. Metabolomics. 2009;6(2):180-190doi: 10.1007/s11306-009-0190-2.
Vaitheesvaran, B., Chueh, F. Y., Xu, J., Trujillo, C., Saad, M. F., Lee, W. N., McGuinness, O. P., & Kurland, I. J. (2010). Advantages of dynamic "closed loop" stable isotope flux phenotyping over static "open loop" clamps in detecting silent genetic and dietary phenotypes. Metabolomics : Official journal of the Metabolomic Society, 6(2), 180-190. https://doi.org/10.1007/s11306-009-0190-2
Vaitheesvaran, Bhavapriya, et al. "Advantages of dynamic "closed loop" stable isotope flux phenotyping over static "open loop" clamps in detecting silent genetic and dietary phenotypes." Metabolomics : Official journal of the Metabolomic Society vol. 6,2 (2010): 180-190. doi: https://doi.org/10.1007/s11306-009-0190-2
Vaitheesvaran B, Chueh FY, Xu J, Trujillo C, Saad MF, Lee WN, McGuinness OP, Kurland IJ. Advantages of dynamic "closed loop" stable isotope flux phenotyping over static "open loop" clamps in detecting silent genetic and dietary phenotypes. Metabolomics. 2010 Jun;6(2):180-190. doi: 10.1007/s11306-009-0190-2. Epub 2009 Nov 12. PMID: 20445758; PMCID: PMC2862950.
Copy Download .nbib Format: NLM
Share it on

Metabolomics. 2010 Jun;6(2):180-190. doi: 10.1007/s11306-009-0190-2. Epub 2009 Nov 12.

Advantages of dynamic "closed loop" stable isotope flux phenotyping over static "open loop" clamps in detecting silent genetic and dietary phenotypes.

Metabolomics : Official journal of the Metabolomic Society

Bhavapriya Vaitheesvaran, Fu-Yu Chueh, Jun Xu, Chuck Trujillo, M F Saad, W N P Lee, Owen P McGuinness, Irwin J Kurland

PMID: 20445758 PMCID: PMC2862950 DOI: 10.1007/s11306-009-0190-2

Abstract

In vivo insulin sensitivity can be assessed using "open loop" clamp or "closed loop" methods. Open loop clamp methods are static, and fix plasma glucose independently from plasma insulin. Closed loop methods are dynamic, and assess glucose disposal in response to a stable isotope labeled glucose tolerance test. Using PPARalpha(-/-) mice, open and closed loop assessments of insulin sensitivity/glucose disposal were compared. Indirect calorimetry done for the assessment of diurnal substrate utilization/metabolic flexibility showed that chow fed PPARalpha(-/-) mice had increased glucose utilization during the light (starved) cycle. Euglycemic clamps showed no differences in insulin stimulated glucose disposal, whether for chow or high fat diets, but did show differences in basal glucose clearance for chow fed PPARalpha(-/-) versus SV129J-wt mice. In contrast, the dynamic stable isotope labeled glucose tolerance tests reveal enhanced glucose disposal for PPARalpha(-/-) versus SV129J-wt, for chow and high fat diets. Area under the curve for plasma labeled and unlabeled glucose for PPARalpha(-/-) was approximately 1.7-fold lower, P < 0.01 during the stable isotope labeled glucose tolerance test for both diets. Area under the curve for plasma insulin was 5-fold less for the chow fed SV129J-wt (P < 0.01) but showed no difference on a high fat diet (0.30 +/- 0.1 for SV129J-wt vs. 0.13 +/- 0.10 for PPARalpha(-/-), P = 0.28). This study demonstrates that dynamic stable isotope labeled glucose tolerance test can assess "silent" metabolic phenotypes, not detectable by the static, "open loop", euglycemic or hyperglycemic clamps. Both open loop and closed loop methods may describe different aspects of metabolic inflexibility and insulin sensitivity.

References

  1. Physiol Rev. 2006 Apr;86(2):465-514 - PubMed
  2. Diabetes. 2006 Feb;55(2):390-7 - PubMed
  3. Endocrinology. 2004 Mar;145(3):1087-95 - PubMed
  4. Diabetes. 2000 May;49(5):677-83 - PubMed
  5. Anal Biochem. 2003 Apr 15;315(2):238-46 - PubMed
  6. Diabetes. 2006 Dec;55(12):3429-38 - PubMed
  7. J Biol Chem. 2002 Dec 27;277(52):50237-44 - PubMed
  8. Biochem Soc Trans. 1986 Oct;14(5):799-806 - PubMed
  9. Cell Metab. 2006 Jan;3(1):35-45 - PubMed
  10. Am J Med. 2006 May;119(5 Suppl 1):S10-6 - PubMed
  11. Proc Nutr Soc. 1995 Mar;54(1):317-27 - PubMed
  12. Diabetes. 2001 Dec;50(12):2809-14 - PubMed
  13. Int J Obes (Lond). 2008 Dec;32 Suppl 7:S109-19 - PubMed
  14. Diabetes. 2006 Dec;55(12):3372-80 - PubMed
  15. Endocrinology. 2004 Apr;145(4):1662-7 - PubMed
  16. Endocrinology. 2005 Jan;146(1):375-82 - PubMed
  17. J Clin Invest. 2000 Jul;106(2):171-6 - PubMed
  18. Physiol Rev. 2006 Jan;86(1):205-43 - PubMed
  19. J Clin Invest. 2005 Jul;115(7):1699-702 - PubMed

Publication Types

Grant support