Summary
Insulin resistance, the impaired ability of insulin to stimulate glucose utilization, is a major characteristic of type 2 diabetes. Insulin sensitivity can be measured using a variety of techniques that are commonly employed in diabetes research and care. Of these, hyperinsulinemic-euglycemic clamp is the gold-standard method to assess insulin sensitivity. The euglycemic clamp is widely used in clinics and laboratories to measure insulin action on glucose utilization in humans and animals for clinical and basic science research. Incorporation of radioactive-labeled glucose during euglycemic clamps makes it possible to measure glucose metabolism in individual organs. In recent years, euglycemic clamps have been actively performed in transgenic animal models of obesity, diabetes, and its complications, and have significantly advanced our understanding on the etiology and pathogenesis of type 2 diabetes. This chapter describes our standardized methods of the euglycemic clamp and associated surgical and biochemical procedures to measure insulin sensitivity in conscious rodents.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Kahn, C.R. (1994). Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 43, 10661084
Reaven, G.M. (1988). Role of insulin resistance in human disease. Diabetes 37, 15951607
DeFronzo, R.A. (1988). The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37, 667687
Haldane, J.B.S., Wigglesworth, V.B., Woodcow, C.E. (1924). Effects of reaction changes on human carbohydrate and oxygen metabolism. Proc Roy Soc Lond, Ser B 96, 1532
Shen, S.-W., Reaven, G.M., Farquhar, J.W. (1970). Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes. J Clin Invest 49, 21512160
DeFronzo, R.A., Beckles, A.D. (1979). Glucose intolerance following chronic metabolic acidosis in man. Am J Physiol 236, E328E334
White, M.F., Kahn, C.R. (1994). The insulin signaling system. J Biol Chem 269, 14
Shepherd, P.R., Kahn, B.B. (1999). Glucose transporters and insulin action - implications for insulin resistance and diabetes melitus. N Engl J Med 341, 248257
Bruning, J.C. (1998). A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 2, 559569
Kim, J.K., Michael, M.D., Previs, S.F., Peroni, O.D., Mauvais-Jarvis, F., Neschen, S., Kahn, B.B., Kahn, C.R., Shulman, G.I. (2000). Redistribution of substrates to adipose tissue in mice with selective insulin resistance in muscle promotes obesity. J Clin Invest 105, 17911797
Kim, H.J., Higashimori, T., Park, S.Y., Choi, H., Dong, J., Kim, Y.J., Noh, H.L., Cho, Y.R., Cline, G., Kim, Y.B., Kim, J.K. (2004). Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes 53, 10601067
Lee, S., Muniyappa, R., Yan, X., Chen, H., Yue, L.Q., Hong, E-G., Kim, J.K., Quon, M.J. (2008). Comparison between surrogate indexes of insulin sensitivity and resistance and hyperinsulinemic euglycemic clamp estimates in mice. Am J Physiol 294, E261E270
Haluzik, M., Columbo, C., Gavrilova, O., Chua, S., Wolf, N., Chen, M., Stannard, B., Dietz, K.R., Le Roith, D., Reitman, M.L. (2004). Genetic background (C57BL/6J versus FVB/N) strongly influences the severity of diabetes and insulin resistance in ob/ob mice. Endocrinology 145, 32583264
Ayala, J.E., Bracy, D.P., McGuinness, O.P., Wasserman, D.H. (2006). Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse. Diabetes 55, 390397
Dubois, M.-J., Bergeron, S., Kim, H.-J., Dombrowski, L., Perreault, M., Fournes, B., Faure, R., Olivier, M., Beauchemin, N., Shulman, G.I., Siminovitch, K.A., Kim, J.K., Marette, A. (2006). The SHP-1 protein tyrosine phosphatase negatively modulates glucose homeostasis. Nat Med 12, 549556
Acknowledgments
This work was supported by grants from the US Public Health Service (U24 DK-59635 and R01 DK-80756), the American Diabetes Association (1-04-RA-47 and 7-07-RA-80), the American Heart Association (0855492D), and the Pennsylvania State Department of Health. I thank Prof. Gerald Shulman for technical advice.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Kim, J.K. (2009). Hyperinsulinemic–Euglycemic Clamp to Assess Insulin Sensitivity In Vivo. In: Stocker, C. (eds) Type 2 Diabetes. Methods in Molecular Biology, vol 560. Humana Press. https://doi.org/10.1007/978-1-59745-448-3_15
Download citation
DOI: https://doi.org/10.1007/978-1-59745-448-3_15
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-934115-15-2
Online ISBN: 978-1-59745-448-3
eBook Packages: Springer Protocols