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Glucose clamp technique: a method for quantifying insulin secretion and resistance

Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.

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				S. R. Kashyap, R. Belfort, R. Berria, S. Suraamornkul, T. Pratipranawatr, J. Finlayson, A. Barrentine, M. Bajaj, L. Mandarino, R. DeFronzo, et al. Discordant effects of a chronic physiological increase in plasma FFA on insulin signaling in healthy subjects with or without a family history of type 2 diabetes Am J Physiol Endocrinol Metab, September 1, 2004; 287(3): E537 - E546. [Abstract] [Full Text] [PDF]

				K. L. Gatford, M. J. De Blasio, P. Thavaneswaran, J. S. Robinson, I. C. McMillen, and J. A. Owens Postnatal ontogeny of glucose homeostasis and insulin action in sheep Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E1050 - E1059. [Abstract] [Full Text] [PDF]

				R. Krogh-Madsen, K. Moller, F. Dela, G. Kronborg, S. Jauffred, and B. K. Pedersen Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-{alpha}, and FFAs to low-dose endotoxemia in humans Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E766 - E772. [Abstract] [Full Text] [PDF]

				A. N. Mazzadi, M. F. Janier, B. Brossier, X. Andre-Fouet, E. McFadden, D. Revel, and P. Croisille Dobutamine-tagged MRI for inotropic reserve assessment in severe CAD: relationship with PET findings Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1946 - H1953. [Abstract] [Full Text] [PDF]

				F. C. Sasso, O. Carbonara, R. Nasti, B. Campana, R. Marfella, M. Torella, G. Nappi, R. Torella, and D. Cozzolino Glucose Metabolism and Coronary Heart Disease in Patients With Normal Glucose Tolerance JAMA, April 21, 2004; 291(15): 1857 - 1863. [Abstract] [Full Text] [PDF]

				Z. Liu, Y. Wu, E. W. Nicklas, L. A. Jahn, W. J. Price, and E. J. Barrett Unlike insulin, amino acids stimulate p70S6K but not GSK-3 or glycogen synthase in human skeletal muscle Am J Physiol Endocrinol Metab, April 1, 2004; 286(4): E523 - E528. [Abstract] [Full Text] [PDF]

				T. Hamada, T. Hayashi, T. Kimura, K. Nakao, and T. Moritani Electrical stimulation of human lower extremities enhances energy consumption, carbohydrate oxidation, and whole body glucose uptake J Appl Physiol, March 1, 2004; 96(3): 911 - 916. [Abstract] [Full Text] [PDF]

				D. E. Kelley, T. M. McKolanis, R. A. F. Hegazi, L. H. Kuller, and S. C. Kalhan Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance Am J Physiol Endocrinol Metab, October 1, 2003; 285(4): E906 - E916. [Abstract] [Full Text] [PDF]

				H. Piloquet, V. Ferchaud-Roucher, F. Duengler, Y. Zair, P. Maugere, and M. Krempf Insulin effects on acetate metabolism Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E561 - E565. [Abstract] [Full Text] [PDF]

				R. E. Van Pelt, W. S. Gozansky, R. S. Schwartz, and W. M. Kohrt Intravenous estrogens increase insulin clearance and action in postmenopausal women Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E311 - E317. [Abstract] [Full Text] [PDF]

				P. M. J. O'Connor, S. R. Kimball, A. Suryawan, J. A. Bush, H. V. Nguyen, L. S. Jefferson, and T. A. Davis Regulation of translation initiation by insulin and amino acids in skeletal muscle of neonatal pigs Am J Physiol Endocrinol Metab, July 1, 2003; 285(1): E40 - E53. [Abstract] [Full Text] [PDF]

				H. A. Koistinen, D. Galuska, A. V. Chibalin, J. Yang, J. R. Zierath, G. D. Holman, and H. Wallberg-Henriksson 5-Amino-Imidazole Carboxamide Riboside Increases Glucose Transport and Cell-Surface GLUT4 Content in Skeletal Muscle From Subjects With Type 2 Diabetes Diabetes, May 1, 2003; 52(5): 1066 - 1072. [Abstract] [Full Text] [PDF]

				M. Takagi, Y. Tanaka, Y. Yamasaki, M. Yamamoto, M. Hori, T. Nakaniwa, M. Niwa, H. Uchino, Y. Tamura, T. Nomiyama, et al. Responsiveness of insulin-induced cardiac sympathetic nerve activation associates with blood pressure regulation in diabetics Am J Physiol Endocrinol Metab, May 1, 2003; 284(5): E1022 - E1026. [Abstract] [Full Text] [PDF]

				D. Komninou, A. Ayonote, J. P. Richie Jr., and B. Rigas Insulin Resistance and Its Contribution to Colon Carcinogenesis Experimental Biology and Medicine, April 1, 2003; 228(4): 396 - 405. [Abstract] [Full Text] [PDF]

				D. F. Bertelli, M. Ueno, M. E. C. Amaral, M. H. Toyama, E. M. Carneiro, S. Marangoni, C. R. O. Carvalho, M. J. A. Saad, L. A. Velloso, and A. C. Boschero Reversal of denervation-induced insulin resistance by SHIP2 protein synthesis blockade Am J Physiol Endocrinol Metab, April 1, 2003; 284(4): E679 - E687. [Abstract] [Full Text] [PDF]

				R. R. Zilkens, V. Burke, G. Watts, L. J. Beilin, and I. B. Puddey The Effect of Alcohol Intake on Insulin Sensitivity in Men: A randomized controlled trial Diabetes Care, March 1, 2003; 26(3): 608 - 612. [Abstract] [Full Text] [PDF]

				S. Dzienis-Straczkowska, M. Straczkowski, M. Szelachowska, A. Stepien, I. Kowalska, and I. Kinalska Soluble Tumor Necrosis Factor-{alpha} Receptors in Young Obese Subjects With Normal and Impaired Glucose Tolerance Diabetes Care, March 1, 2003; 26(3): 875 - 880. [Abstract] [Full Text] [PDF]

				M. Guldstrand, B. Ahren, and U. Adamson Improved beta -cell function after standardized weight reduction in severely obese subjects Am J Physiol Endocrinol Metab, March 1, 2003; 284(3): E557 - E565. [Abstract] [Full Text] [PDF]

				R. K. Krishnan, W. J. Evans, and J. P. Kirwan Impaired substrate oxidation in healthy elderly men after eccentric exercise J Appl Physiol, February 1, 2003; 94(2): 716 - 723. [Abstract] [Full Text] [PDF]

				G. D. Kolovou, D. Ch. Daskalova, S. A. Iraklianou, E. N. Adamopoulou, N. D. Pilatis, G. C. Hatzigeorgiou, and D. V. Cokkinos Postprandial Lipemia in Hypertension J. Am. Coll. Nutr., February 1, 2003; 22(1): 80 - 87. [Abstract] [Full Text] [PDF]

				K. A. Virtanen, K. Hallsten, R. Parkkola, T. Janatuinen, F. Lonnqvist, T. Viljanen, T. Ronnemaa, J. Knuuti, R. Huupponen, P. Lonnroth, et al. Differential Effects of Rosiglitazone and Metformin on Adipose Tissue Distribution and Glucose Uptake in Type 2 Diabetic Subjects Diabetes, February 1, 2003; 52(2): 283 - 290. [Abstract] [Full Text] [PDF]

				R. C. Bonadonna, M. Stumvoll, A. Fritsche, M. Muggeo, H. Haring, E. Bonora, and T. W. van Haeften Altered Homeostatic Adaptation of First- and Second-Phase {beta}-Cell Secretion in the Offspring of Patients With Type 2 Diabetes: Studies With a Minimal Model to Assess {beta}-Cell Function Diabetes, February 1, 2003; 52(2): 470 - 480. [Abstract] [Full Text] [PDF]

				D. E. Flanagan, M. L. Evans, T. P. Monsod, F. Rife, R. A. Heptulla, W. V. Tamborlane, and R. S. Sherwin The influence of insulin on circulating ghrelin Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E313 - E316. [Abstract] [Full Text] [PDF]

				T. T. Tran, N. Gupta, T. Goh, D. Naigamwalla, M. C. Chia, N. Koohestani, S. Mehrotra, G. McKeown-Eyssen, A. Giacca, and W. R. Bruce Direct Measure of Insulin Sensitivity with the Hyperinsulinemic-Euglycemic Clamp and Surrogate Measures of Insulin Sensitivity with the Oral Glucose Tolerance Test: Correlations with Aberrant Crypt Foci Promotion in Rats Cancer Epidemiol. Biomarkers Prev., January 1, 2003; 12(1): 47 - 56. [Abstract] [Full Text] [PDF]