A model of the kinetics of insulin in man
Open accessAbstract
The design of the present study of the kinetics of insulin in man combines experimental features which obviate two of the major problems in previous insulin studies. (a) The use of radioiodinated insulin as a tracer has been shown to be inappropriate since its metabolism differs markedly from that of the native hormone. Therefore porcine insulin was administered by procedures which raised insulin levels in arterial plasma into the upper physiologic range. Hypoglycemia was prevented by adjusting the rate of an intravenous infusion of glucose in order to control the blood glucose concentration (the glucose-clamp technique). (b) Estimation of a single biological half-time of insulin after pulse injection of the hormone has been shown to be inappropriate since plasma insulin disappearance curves are multiexponential. Therefore the SAAM 25 computer program was used in order to define the parameters of a three compartment insulin model. The combined insulin mass of the three compartments (expressed as plasma equivalent volume) is equal to inulin space (15.7% body wt). Compartment 1 is apparently the plasma space (4.5%). The other two compartments are extra-vascular; compartment 2 is small (1.7%) and equilibrates rapidly with plasma, and compartment 3 is large (9.5%) and equilibrates slowly with plasma. The SAAM 25 program can simulate the buildup and decay of insulin in compartments 2 and 3 which cannot be assayed directly. Insulin in compartment 3 was found to correlate remarkably with the time-course of the servo-controlled glucose infusion. Under conditions of a steady-state arterial glucose level, glucose infusion is a measure of glucose utilization. We conclude that compartment 3 insulin (rather than plasma insulin) is a more direct determinant of glucose utilization. We suggest that the combined use of glucose-clamp and kinetic-modeling techniques should aid in the delineation of pathophysiologic states affecting glucose and insulin metabolism.
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Multiple compartments provide the best model for insulin.
“Many authors [13, 14] have demonstrated that insulin is best modeled using multiple compartments.”
From Pharmacokinetic modeling of the glucoregulatory system (2008) · cites this paper as [14]
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DENSITOMETRIC ANALYSIS OF BODY COMPOSITION: REVISION OF SOME QUANTITATIVE ASSUMPTIONS*
Brožek, J., Grande, F., Anderson, J. T., & Keys, A. B. (1963) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1963.tb17079.x · Cited by 2,263 · see citing works
Berson, S. A., Yalow, R. S., Bauman, A., Rothschild, M. A., & Newerly, K. (1956) · Journal of Clinical Investigation · doi:10.1172/jci103262 · Cited by 836 · see citing works
Greenway, C. V., & Stark, R. D. (1971) · Physiological Reviews · doi:10.1152/physrev.1971.51.1.23 · Cited by 638 · see citing works
Morphological classifications of vertebrate blood capillaries
Bennett, H. S., Luft, J. H., & Hampton, J. C. (1959) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1959.196.2.381 · Cited by 635 · see citing works
The Routine Fitting of Kinetic Data to Models
Berman, M., Shahn, E., & Weiss, M. F. (1962) · Biophysical Journal · doi:10.1016/s0006-3495(62)86855-6 · Cited by 335 · see citing works
Self-citationInvariants in Experimental Data on Linear Kinetics and the Formulation of Models
Berman, M., & Schoenfeld, R. L. (1956) · Journal of Applied Physics · doi:10.1063/1.1722264 · Cited by 278 · see citing works
Self-citationPortal and Peripheral Vein Immunoreactive Insulin Concentrations Before and After Glucose Infusion
Blackard, W. G., & Nelson, N. C. (1970) · Diabetes · doi:10.2337/diab.19.5.302 · Cited by 247 · see citing works
Andres, R. (1971) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)32479-8 · Cited by 232 · see citing works
Self-citationRegional differences in capillary permeability
Mayerson, H. S., Wolfram, C. G., Shirley, H. H., & Wasserman, K. (1960) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1960.198.1.155 · Cited by 206 · see citing works
Carbohydrate Metabolism in Uremia
Horton, E. S., JOHNSON, C., & LEBOVITZ, H. E. (1968) · Annals of Internal Medicine · doi:10.7326/0003-4819-68-1-63 · Cited by 193 · see citing works
Iversen, J., & Miles, D. W. (1971) · Diabetes · doi:10.2337/diab.20.1.1 · Cited by 180 · see citing works
The Renal Handling of Insulin*
Chamberlain, M. J., & Stimmler, L. (1967) · Journal of Clinical Investigation · doi:10.1172/jci105597 · Cited by 176 · see citing works
Effect of Human Growth Hormone on Muscle and Adipose Tissue Metabolism in the Forearm of Man *
Rabinowitz, D., Klassen, G. A., & Zierler, K. L. (1965) · Journal of Clinical Investigation · doi:10.1172/jci105126 · Cited by 156 · see citing works
Samols, E., & Ryder, J. A. (1961) · Journal of Clinical Investigation · doi:10.1172/jci104435 · Cited by 140 · see citing works
Measurement of the Insulin Delivery Rate in Man
Turner, R. C., Grayburn, J. A., Newman, G. B., & Nabarro, J. D. N. (1971) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-33-2-279 · Cited by 121 · see citing works
Inhibition by insulin of hepatic glucose production in the normal dog
Steele, R., Bishop, J. S., Dunn, A., ALTSZULER, N., Rathgeb, I., & de Bodo, R. C. (1965) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1965.208.2.301 · Cited by 111 · see citing works
GROWTH-HORMONE AND CORTISOL RESPONSES TO INSULIN INFUSION IN PATIENTS WITH DIABETES MELLITUS
Sönksen, P. H., Srivastava, M. C., Tompkins, C. V., & Nabarro, J. D. N. (1972) · The Lancet · doi:10.1016/s0140-6736(72)91328-1 · Cited by 106 · see citing works
Madison, L. L., Combes, B., Adams, R. H., & Strickland, W. (1960) · Journal of Clinical Investigation · doi:10.1172/jci104065 · Cited by 104 · see citing works
Nomenclature for Tracer Kinetics
Brownell, G. L., Berman, M., & Robertson, J. S. (1968) · The International Journal of Applied Radiation and Isotopes · doi:10.1016/0020-708x(68)90022-7 · Cited by 99 · see citing works
Self-citationMortimore, G. E., & Tietze, F. (1959) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1959.tb44913.x · Cited by 89 · see citing works
Metabolic clearance of insulin in man
Genuth, S. M. (1972) · Diabetes · doi:10.2337/diab.21.10.1003 · Cited by 72 · see citing works
Derivation of a three compartment model describing disappearance of plasma insulin-131I in man
Silvers, A., Swenson, R. S., Farquhar, J. W., & Reaven, G. M. (1969) · Journal of Clinical Investigation · doi:10.1172/jci106112 · Cited by 70 · see citing works
Proinsulin and C-Peptide in Blood
Rubenstein, A. H., Block, M. B., Starr, J. I., Melani, F., & Steiner, D. F. (1972) · Diabetes · doi:10.2337/diab.21.2.s661 · Cited by 70 · see citing works
Madison, L. L., Combes, B., Unger, R. H., & Kaplan, N. M. (1959) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1959.tb39579.x · Cited by 69 · see citing works
Diffusion of Glucose, Insulin, Inulin, and Evans Blue Protein into Thoracic Duct Lymph of Man*
Rasio, E., Hampers, C. L., Soeldner, J. S., & Cahill, G. F. (1967) · Journal of Clinical Investigation · doi:10.1172/jci105596 · Cited by 69 · see citing works
Ørskov, H., & Christensen, N. J. (1969) · Diabetes · doi:10.2337/diab.18.10.653 · Cited by 69 · see citing works
Insulin Secretion by Isolated Islets in Presence of Glucose, Insulin and Anti-Insulin Serum
Malaisse, W. J., MALAISSE-LAGAE, F., Lacy, P. E., & Wright, P. H. (1967) · Experimental Biology and Medicine · doi:10.3181/00379727-124-31773 · Cited by 68 · see citing works
Insulin delivery rate into plasma in normal and diabetic subjects
D, M. P. S. M., Farquhar, J. W., Silvers, A., & Reaven, G. M. (1968) · Journal of Clinical Investigation · doi:10.1172/jci105884 · Cited by 62 · see citing works
Izzo, J. L., Bartlett, J. W., Roncone, A. M., Izzo, M. J., & Bale, W. F. (1967) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)95968-5 · Cited by 60 · see citing works
Relation of Blood Volume and Cardiac Output to Body Type
Gregersen, M. I., & Nickerson, J. L. (1950) · Journal of Applied Physiology · doi:10.1152/jappl.1950.3.6.329 · Cited by 54 · see citing works
Evidence for an Insulin-Induced Inhibition of Insulin Release by Isolated Islets of Langerhans
Sodoyez, J. C., Sodoyez‐Goffaux, F., & Foe, P. P. (1969) · Experimental Biology and Medicine · doi:10.3181/00379727-130-33608 · Cited by 53 · see citing works
PLASMA VOLUME AND THIOCYANATE SPACE IN FAMINE EDEMA AND RECOVERY
Henschel, A. F., Mickelsen, O., TAYLOR, H. L., & Keys, A. B. (1947) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1947.150.1.170 · Cited by 52 · see citing works
Pj, T., Spafford, N. R., & Blaw, M. E. (1953) · PubMed · Cited by 48 · see citing works
[Factors influencing different rates of insulin release in vitro].
Gm, G., Curry, D., Bennett, L. L., & Jj, R. (1968) · PubMed · Cited by 45 · see citing works
Insulin Half-Life in Normal and Diabetic Subjects.
Tomasi, T. B., Sledz, D., Wales, J. K., & Recant, L. (1967) · Experimental Biology and Medicine · doi:10.3181/00379727-126-43434 · Cited by 39 · see citing works
Disappearance of Immunoreactive Insulin in Normal and Adult-onset Diabetic Subjects
Stimmler, L. (1967) · Diabetes · doi:10.2337/diab.16.9.652 · Cited by 38 · see citing works
DISAPPEARANCE-RATE OF EXOGENOUS HUMAN INSULIN
Ørskov, H., & Christensen, N. J. (1966) · The Lancet · doi:10.1016/s0140-6736(66)92865-0 · Cited by 38 · see citing works
Rappaport, A. M., OHIRA, S., Coddling, J. A., EMPEY, G., KALNINS, A., Lin, B. J., & Haist, R. E. (1972) · Endocrinology · doi:10.1210/endo-91-1-168 · Cited by 37 · see citing works
Plasma insulin after diversion of portal and pancreatic venous blood to vena cava.
Waddell, W. R., & Sussman, K. E. (1967) · Journal of Applied Physiology · doi:10.1152/jappl.1967.22.4.808 · Cited by 37 · see citing works
Passage of Insulin and Inulin Across Vascular Membranes in the Dog
Rasio, E., Mack, E. J., Egdahl, R. H., & Herrera, M. G. (1968) · Diabetes · doi:10.2337/diab.17.11.668 · Cited by 36 · see citing works
Steady State Plasma Insulin Response to Continuous Glucose Infusion in Normal and Diabetic Subjects
Reaven, G. M., Farquhar, J. W., & Nakanishi, R. H. (1969) · Diabetes · doi:10.2337/diab.18.5.273 · Cited by 34 · see citing works
Stimmler, L., MASHITER, K., Snodgrass, G. J. A. I., Boucher, B. J., & Abrams, M. E. (1972) · Clinical Science · doi:10.1042/cs0420337 · Cited by 30 · see citing works
Rasio, E., Whichelow, M. J., Butterfield, W. J. H., & Hicks, B. H. (1972) · Diabetologia · doi:10.1007/bf01225567 · Cited by 29 · see citing works
The half-life of endogenous serum immunoreactive insulin in man
Williams, R. F., Gleason, R. E., & Soeldner, J. S. (1968) · Metabolism · doi:10.1016/0026-0495(68)90009-7 · Cited by 25 · see citing works
SIGNIFICANCE OF DISAPPEARANCE-RATE OF INJECTED INSULIN
Martin, F. I. R., Stocks, A. E., & Pearson, M. J. (1967) · The Lancet · doi:10.1016/s0140-6736(67)90469-2 · Cited by 23 · see citing works
Cardiac output and regional blood flow
Samet, P. (1963) · The American Journal of Cardiology · doi:10.1016/0002-9149(63)90094-8 · Cited by 22 · see citing works
A Semiautomated Technic for Radioimmunoassay: Double Antibody Assay of Insulin
Haas, M. L., Shenkman, L., Weissman, P. N., & Andres, R. (1970) · Diabetes · doi:10.2337/diab.19.2.127 · Cited by 2 · see citing works
Self-citationTHE FEDERATION OF AMERICAN SOCIETIES FOR EXPERIMENTAL BIOLOGY
(1938) · Science · doi:10.1126/science.87.2257.295 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028 · see citing works
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425 · see citing works
“As described in a previous publication (17), this theory could be tested by subjecting the data to kinetic analysis (9).”
BackgroundMethodInfluentialSelf-citationBergman, R. N., Phillips, L. S., & Cobelli, C. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110398 · Cited by 1,640 · see citing works
The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man.
DeFronzo, R. A., Cooke, C. R., Andres, R., Faloona, G. R., & Davis, P. J. (1975) · Journal of Clinical Investigation · doi:10.1172/jci107996 · Cited by 1,113 · see citing works
“to six normal volunteer subjects while maintaining the blood glucose concentration at the fasting level by a negative feedback servocontrol mechanism (27) which allows the frequent adjustment of a variable glucose infusion to maintain constant blood glucose concentration.”
BackgroundSelf-citationAssessment of Insulin Sensitivityin Vivo*
Bergman, R. N., Finegood, D. T., & Ader, M. (1985) · Endocrine Reviews · doi:10.1210/edrv-6-1-45 · Cited by 1,062 · see citing works
Insulin resistance, insulin insensitivity, and insulin unresponsiveness: A necessary distinction
Kahn, C. R. (1978) · Metabolism · doi:10.1016/s0026-0495(78)80007-9 · Cited by 793 · see citing works
Bergman, R. N., Prager, R., Volund, A., & Olefsky, J. M. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112886 · Cited by 772 · see citing works
“One of the primary simplifications implemented in the model is that during the FSIGT, glucose distribution can be described by a single compartment representation, despite evidence for three-compartment distribution of labeled glucose moieties when sufficient time is allotted (30, 31).”
RIZZA, R. A., MANDARINO, L. J., & GERICH, J. E. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-54-1-131 · Cited by 696 · see citing works
Dose-response characteristics for effects of insulin on production and utilization of glucose in man
Rizza, R. A., Mandarino, L. J., & Gerich, J. E. (1981) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1981.240.6.e630 · Cited by 703 · see citing works
Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects.
Kolterman, O. G., Insel, J., Saekow, M., & Olefsky, J. M. (1980) · Journal of Clinical Investigation · doi:10.1172/jci109790 · Cited by 664 · see citing works
Kolterman, O., Gray, R. S., Griffin, J., BURSTEIN, P. J., Insel, J. R., Scarlett, J. A., & Olefsky, J. M. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110350 · Cited by 629 · see citing works
Mechanisms of Insulin Resistance in Aging
Fink, R. I., Kolterman, O., Griffin, J., & Olefsky, J. M. (1983) · Journal of Clinical Investigation · doi:10.1172/jci110908 · Cited by 555 · see citing works
Diabetes: Models, Signals, and Control
Cobelli, C., Dalla Man, C., Sparacino, G., Magni, L., De Nicolao, G., & Kovatchev, B. P. (2009) · IEEE Reviews in Biomedical Engineering · doi:10.1109/rbme.2009.2036073 · Cited by 511 · see citing works
“This was a model ingredient requested by data and modeling methodology, in agreement with [24].”
Age-related changes in glucose metabolism, hyperglycemia, and cardiovascular risk
Chia, C. W., Egan, J. M., & Ferrucci, L. (2018) · Circulation Research · doi:10.1161/circresaha.118.312806 · Cited by 454 · see citing works
The effects of glucose and insulin on renal electrolyte transport.
DeFronzo, R. A., Goldberg, M., & Agus, Z. S. (1976) · Journal of Clinical Investigation · doi:10.1172/jci108463 · Cited by 454 · see citing works
Kubota, T., Kubota, N., Kumagai, H., Yamaguchi, S., Kozono, H., Takahashi, T., Inoue, M., Itoh, S., Takamoto, I., Sasako, T., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.018 · Cited by 435 · see citing works
“Recent evidence indicates that insulin delivery to the skeletal muscle interstitium is the ratelimiting step in insulin-stimulated glucose uptake by the skeletal muscle, and is much slower in obese insulin-resistant subjects than in normal subjects (Sherwin et al., 1974; DeFronzo et al., 1979; Yang et al., 1989; Janss…”
BackgroundInfluentialBuchanan, T. A., Metzger, B. E., Freinkel, N., & Bergman, R. N. (1990) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(90)91306-w · Cited by 425 · see citing works
Considerations in the Design of Hyperinsulinemic-Euglycemic Clamps in the Conscious Mouse
Ayala, J. E., Bracy, D. P., McGuinness, O. P., & Wasserman, D. H. (2006) · Diabetes · doi:10.2337/diabetes.55.02.06.db05-0686 · Cited by 399 · see citing works
“6% body wt) and the approximate plasma and interstitial fluid volume (25% body wt) (31).”
BackgroundMechanisms of Insulin Resistance Following Injury
Black, P. R., Brooks, D. C., Bessey, P. Q., Wolfe, R. R., & Wilmore, D. W. (1982) · Annals of Surgery · doi:10.1097/00000658-198210000-00005 · Cited by 379 · see citing works
Prehepatic Insulin Production in Man: Kinetic Analysis Using Peripheral Connecting Peptide Behavior*
EATON, R. P., ALLEN, R. C., SCHADE, D. S., ERICKSON, K. M., & STANDEFER, J. (1980) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-51-3-520 · Cited by 363 · see citing works
Polonsky, K. S., Licinio-Paixao, J., Given, B. D., Pugh, W., Rue, P., Galloway, J., Karrison, T., & Frank, B. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112308 · Cited by 359 · see citing works
“(36) have proposed a threecompartment model for the kinetic analysis of insulin.”
BackgroundBlood flow and muscle metabolism: a focus on insulin action
Clark, M. G., Wallis, M. G., Barrett, E. J., Keske, M. A., Richards, S. M., Clerk, L. H., & Rattigan, S. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00408.2002 · Cited by 355 · see citing works
“There is a delay in the onset of insulin action in vivo compared with that in vitro (129, 157, 196), which may be due to transendothelial insulin transport.”
BackgroundBarrett, E. J., Eggleston, E. M., Inyard, A. C., Wang, H., Li, G., Chai, W., & Liu, Z. (2009) · Diabetologia · doi:10.1007/s00125-009-1313-z · Cited by 323 · see citing works
“In the 1970s, Andres and colleagues published a series of studies directed at assessing the kinetics of porcine insulin handling in humans [1-3].”
BackgroundObesity and diet affect glucose dynamics and insulin sensitivity in Thoroughbred geldings1
Hoffman, R. M., Boston, R. C., Stefanovski, D., Kronfeld, D. S., & Harris, P. A. (2003) · Journal of Animal Science · doi:10.2527/2003.8192333x · Cited by 321 · see citing works
Mechanisms of insulin resistance in obesity and noninsulin-dependent (type II) diabetes
Olefsky, J. M., & Kolterman, O. (1981) · The American Journal of Medicine · doi:10.1016/0002-9343(81)90422-8 · Cited by 305 · see citing works
DeFronzo, R. A., Tobin, J. D., Rowe, J. W., & Andres, R. (1978) · Journal of Clinical Investigation · doi:10.1172/jci109144 · Cited by 305 · see citing works
Self-citationThe evolution of β‐cell dysfunction and insulin resistance in type 2 diabetes
Bergman, R. N., Finegood, D. T., & Kahn, S. E. (2002) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.32.s3.5.x · Cited by 302 · see citing works
DeFronzo, R. A., Ferrannini, E., Hendler, R., Wahren, J., & Felig, P. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.10.5173 · Cited by 296 · see citing works
Insulin Sensitivity and Its Measurement: Structural Commonalities among the Methods1
Radziuk, J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.12.7025 · Cited by 289 · see citing works
Insulin action and resistance in obesity and noninsulin-dependent type II diabetes mellitus
Olefsky, J. M., Kolterman, O., & Scarlett, J. A. (1982) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1982.243.1.e15 · Cited by 277 · see citing works
Experimental validation of measurements of glucose turnover in nonsteady state.
Radziuk, J., Norwich, K. H., & Vranic, M. (1978) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1978.234.1.e84 · Cited by 277 · see citing works
Microvascular Function Relates to Insulin Sensitivity and Blood Pressure in Normal Subjects
Serné, E. H., Stehouwer, C. D. A., ter Maaten, J. C., ter Wee, P. M., Rauwerda, H., Donker, A. J. M., & Gans, R. O. B. (1999) · Circulation · doi:10.1161/01.cir.99.7.896 · Cited by 263 · see citing works
Insulin Binding to Monocytes and Insulin Action in Human Obesity, Starvation, and Refeeding
Defronzo, R. A., Soman, V., Sherwin, R. S., Hendler, R., & Felig, P. (1978) · Journal of Clinical Investigation · doi:10.1172/jci109108 · Cited by 252 · see citing works
Self-citationRetractedInsulin Control of Glucose Metabolism in Man
Insel, P. A., Liljenquist, J. E., Tobin, J. D., Sherwin, R. S., Watkins, P., Andres, R., & Berman, M. (1975) · Journal of Clinical Investigation · doi:10.1172/jci108006 · Cited by 244 · see citing works
Self-citationOral Glucose Augmentation of Insulin Secretion
Andersen, D. K., Elahi, D., Brown, J. C., Tobin, J. D., & Andres, R. (1978) · Journal of Clinical Investigation · doi:10.1172/jci109100 · Cited by 239 · see citing works
Self-citationCampbell, P. J., Mandarino, L. J., & Gerich, J. E. (1988) · Metabolism · doi:10.1016/0026-0495(88)90023-6 · Cited by 226 · see citing works
Insulin transport across capillaries is rate limiting for insulin action in dogs.
Yang, Y. J., Hope, I. D., Ader, M., & Bergman, R. N. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114339 · Cited by 303 · see citing works
Splanchnic and renal metabolism of insulin in human subjects: a dose-response study
Ferrannini, E., Wahren, J., FABER, O. K., Felig, P., Binder, C., & DeFronzo, R. A. (1983) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1983.244.6.e517 · Cited by 214 · see citing works
Renal Handling of Urate and Sodium during Acute Physiological Hyperinsulinaemia in Healthy Subjects
ter Maaten, J. C., Voorburg, A., Heine, R. J., ter Wee, P. M., Donker, A. J. M., & Gans, R. O. B. (1997) · Clinical Science · doi:10.1042/cs0920051 · Cited by 210 · see citing works
Obesity and insulin resistance: Lessons learned from the Pima indians
Lillioja, S., & Bogardus, C. (1988) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610040508 · Cited by 203 · see citing works
Prager, R., Wallace, P., & Olefsky, J. M. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112599 · Cited by 204 · see citing works
Insulin Metabolism and Degradation*
Duckworth, W. C., & Kitabchi, A. E. (1981) · Endocrine Reviews · doi:10.1210/edrv-2-2-210 · Cited by 199 · see citing works
The Effect of Insulin Feedback on Closed Loop Glucose Control
Steil, G. M., Palerm, C. C., Kurtz, N., Voskanyan, G. R., Roy, A., Paz, S., & KANDEEL, F. R. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2578 · Cited by 195 · see citing works
“The present study assessed the ability of an insulin PK model (13) to predict the plasma insulin profile obtained with sc insulin delivery and whether feedback of the profile would allow acceptable closed-loop meal responses to be obtained in humans.”
MethodInsulin Sensitivity and Insulin Binding to Monocytes in Maturity-Onset Diabetes
Defronzo, R., Deibert, D., Hendler, R., Felig, P., & Soman, V. (1979) · Journal of Clinical Investigation · doi:10.1172/jci109394 · Cited by 188 · see citing works
RetractedClark, M. G. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90477.2008 · Cited by 188 · see citing works
“There are a number of studies indicating insulin’s transendothelial transport to be rate limiting for its action in stimulating muscle glucose uptake (103, 124, 159, 189).”
BackgroundAn integrated mathematical model of the dynamics of blood glucose and its hormonal control
Cobelli, C., Federspil, G., Pacini, G., Salvan, A., & Scandellari, C. (1982) · Mathematical Biosciences · doi:10.1016/0025-5564(82)90050-5 · Cited by 182 · see citing works
Diabetic ketoacidosis: new concepts and trends in pathogenesis and treatment
KREISBERG, R. A. (1978) · Annals of Internal Medicine · doi:10.7326/0003-4819-88-5-681 · Cited by 179 · see citing works
First-phase insulin secretion: does it exist in real life? Considerations on shape and function
Caumo, A., & Luzi, L. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00139.2003 · Cited by 174 · see citing works
Davis, S. N., Shavers, C., Costa, F., & Mosqueda-Garcia, R. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118839 · Cited by 173 · see citing works
Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature
Barrett, E. J., Wang, H., Upchurch, C. T., & Liu, Z. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00186.2011 · Cited by 171 · see citing works
Feedback inhibition of insulin secretion by insulin: relation to the hyperinsulinemia of obesity
Elahi, D., Nagulesparan, M., Hershcopf, R. J., Muller, D. C., Tobin, J. D., Blix, P. M., Rubenstein, A. H., Unger, R. H., & Andres, R. (1982) · New England Journal of Medicine · doi:10.1056/nejm198205203062002 · Cited by 210 · see citing works
Self-citationStochastic modelling of insulin sensitivity and adaptive glycemic control for critical care
Lin, J., Lee, D., Chase, J. G., Shaw, G. M., Compte, A. L., Lotz, T., Wong, J., Lonergan, T., & Hann, C. E. (2007) · Computer Methods and Programs in Biomedicine · doi:10.1016/j.cmpb.2007.04.006 · Cited by 163 · see citing works
“Assumptions for these responses could also compromise control accuracy, as both endogenous insulin and glucose productions are known to vary significantly between patients [25-29] and over time.”
BackgroundKanderian, S. S., WEINZIMER, S. A., Voskanyan, G. R., & Steil, G. M. (2009) · Journal of Diabetes Science and Technology · doi:10.1177/193229680900300508 · Cited by 162 · see citing works
Systemic delivery of therapeutic peptides and proteins
Banga, A. K., & CHIEN, Y. (1988) · International Journal of Pharmaceutics · doi:10.1016/0378-5173(88)90246-3 · Cited by 156 · see citing works
Castillo, C., Bogardus, C., Bergman, R. N., Thuillez, P., & Lillioja, S. (1994) · Journal of Clinical Investigation · doi:10.1172/jci116932 · Cited by 154 · see citing works
Cobelli, C., TOFFOLO, G. M., & Ferrannini, E. (1984) · Mathematical Biosciences · doi:10.1016/0025-5564(84)90114-7 · Cited by 151 · see citing works
Hepatic Removal of Insulin in Normal Man: Dose Response to Endogenous Insulin Secretion*
Eaton, R. P., Allen, R. C., & Schade, D. S. (1983) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-56-6-1294 · Cited by 150 · see citing works
Waldh�usl, W., Bratusch-Marrain, P. R., Gasic, S., Korn, A., & Nowotny, P. (1979) · Diabetologia · doi:10.1007/bf01235858 · Cited by 149 · see citing works
“Thus estimates of insulin release were obtained previously by using a model of the kinetics of insulin in man [3, 24].”
BackgroundMethodInfluentialGalassetti, P. R., Tate, D. B., Neill, R. A., Morrey, S., Wasserman, D. H., & Davis, S. N. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1761 · Cited by 146 · see citing works
“At 120 min, in all studies, a primed continuous infusion of insulin (9 pmol kg 1 min (1)) was started (18).”
Cobelli, C., & Mari, A. (1983) · Medical & Biological Engineering & Computing · doi:10.1007/bf02442625 · Cited by 140 · see citing works
Jauch, K. ‐., Hartl, W. H., Guenther, B., WICKLMAYR, M., Kristian, R. E. T. T., & Dietze, G. (1987) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1987.tb01141.x · Cited by 140 · see citing works
Assessment of insulin sensitivity in vivo: A critical review
Bergman, R. N., Hope, I. D., Yang, Y. J., Watanabe, R. M., Meador, M. A., Youn, J. H., & Ader, M. (1989) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610050501 · Cited by 135 · see citing works
Vicini, P., Caumo, A., & Cobelli, C. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.5.e1024 · Cited by 129 · see citing works
“Insulin-dependent glucose disposal occurs in the slowly exchanging pool and is assumed to be parametrically controlled, not by plasma, but by insulin in a remote compartment (13).”
BackgroundBell, K. J., Toschi, E., Steil, G. M., & Wolpert, H. A. (2016) · Diabetes Care · doi:10.2337/dc15-2855 · Cited by 121 · see citing works
“First, a metabolic model comprised of an insulin pharmacokinetic/ pharmacodynamic submodel (2), the Bergman minimal model (3,4), and a meal absorption model (5) was identified using a nonlinear generalized reduced gradient algorithm available in”
MethodInsulin secretion and action in patients with pancreatic cancer
Cersósimo, E., Pisters, P. W. T., Pesola, G. R., McDermott, K., Bajorunas, D. R., & Brennan, M. F. (1991) · Cancer · doi:10.1002/1097-0142(19910115)67:2 · Cited by 119 · see citing works
Endothelial cell barriers: Transport of molecules between blood and tissues
Yazdani, S., Jaldín‐Fincati, J. R., Pereira, R. V. S., & Klip, A. (2019) · Traffic · doi:10.1111/tra.12645 · Cited by 118 · see citing works
“Insulin in particular is cleared out of tissues as part of the mechanism to terminate its action, and for years it has been postulated that the interstitium of muscle and adipose tissues constitute an insulin compartment important for glucose utilization.(50,77) Hence, the rate of insulin removal from the interstitium…”
BackgroundTura, A., Ludvik, B. H., Nolan, J. J., Pacini, G., & Thomaseth, K. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.5.e966 · Cited by 120 · see citing works
“The model presented in this study also allows estimation of systemic insulin clearance; that in the original version (23) was fixed to values obtained from other studies (10–12) or from the literature (18, 21).”
Pathophysiology of Diabetes Mellitus
Sherwin, R., & Felig, P. (1978) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)31766-7 · Cited by 120 · see citing works
Self-citationChronic hyperinsulinemia and blood pressure. Interaction with catecholamines?
Hall, J. E., Brands, M. W., Kivlighn, S. D., Mizelle, H. L., Hildebrandt, D. A., & Gaillard, C. A. (1990) · Hypertension · doi:10.1161/01.hyp.15.5.519 · Cited by 116 · see citing works
The kinetics of insulin in man. II. Role of the liver
Ferrannini, E., & Cobelli, C. (1987) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610030202 · Cited by 115 · see citing works
Influence of hyperglycemia on insulin's in vivo effects in type II diabetes.
REVERS, R. R., Fink, R. I., Griffin, J., Olefsky, J. M., & Kolterman, O. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111258 · Cited by 115 · see citing works
Glucose homeostasis during prolonged suppression of glucagon and insulin secretion by somatostatin.
Sherwin, R. S., Hendler, R., DeFronzo, R. A., Wahren, J., & Felic, P. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.1.348 · Cited by 110 · see citing works
Self-citationEffects of antecedent prolonged exercise on subsequent counterregulatory responses to hypoglycemia
Galassetti, P. R., Mann, S. L., Tate, D. B., Neill, R. A., da Costa, F. A. A., Wasserman, D. H., & Davis, S. N. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.6.e908 · Cited by 108 · see citing works
“5 mU zkg21 zmin21) was started (38), and the rate of fall of plasma glucose was controlled so that the target hypoglycemic plateau (;54 mg/dl) was reached by t 5 30 min and was maintained until the end of the experimental period.”
BackgroundInsulin Responsiveness of Adipose Tissue Lipoprotein Lipase Is Delayed but Preserved in Obesity*
SADUR, U. N., Yost, T. J., & Eckel, R. H. (1984) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-59-6-1176 · Cited by 106 · see citing works
Unger, R. H. (2008) · JAMA · doi:10.1001/jama.299.10.1185 · Cited by 103 · see citing works
Resistive Training Increases Insulin Action in Postmenopausal Women
Ryan, A. S., Pratley, R., Goldberg, A. P., & Elahi, D. (1996) · The Journals of Gerontology Series A · doi:10.1093/gerona/51a.5.m199 · Cited by 104 · see citing works
“Insulin leaves the plasma compartment to exert its action at the tissue level; this concentration of insulin at the tissue level was estimated using the previously described model where the insulin concentration at the tissue level is referred to as I3 (compartment 3) (18).”
BackgroundMethodSingh, R., Aguiar, R. B. D., Naik, S., Mani, S., Ostadsharif, K., Wencker, D., Sotoudeh, M., Malekzadeh, R., Sherwin, R. S., & Mani, A. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.01.009 · Cited by 98 · see citing works
“Glucose kinetics were determined in the basal state and during euglycemic hyperinsulinemia (Sherwin et al., 1974).”
Self-citationPelikánová, T., Kohout, M., Válek, J., Baše, J., & Kazdová, L. (1989) · Metabolism · doi:10.1016/0026-0495(89)90261-8 · Cited by 103 · see citing works
Davis, S. N., Mann, S., Galassetti, P., Neill, R. A., Tate, D., Ertl, A. C., & Costa, F. (2000) · Diabetes · doi:10.2337/diabetes.49.11.1897 · Cited by 100 · see citing works
“At time zero, a primed continuous infusion of insulin (12) was administered at a rate of 9 pmol · kg · min for 120 min.”
MethodDavis, S. N., Shavers, C., Davis, B. A., & Costa, F. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119550 · Cited by 94 · see citing works
The protein-sparing effect of carbohydrate
Fuller, M. F., & Crofts, R. M. J. (1977) · British Journal Of Nutrition · doi:10.1079/bjn19770113 · Cited by 98 · see citing works
Sintov, A. C., Levy, H. V., & Botner, S. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.08.004 · Cited by 97 · see citing works
Insulin responses to varying profiles of subcutaneous insulin infusion: kinetic modelling studies
Kraegen, E. W., & Chisholm, D. J. (1984) · Diabetologia · doi:10.1007/bf00252409 · Cited by 96 · see citing works
The diagnosis of equine insulin dysregulation
Bertin, F., & de Laat, M. A. (2017) · Equine Veterinary Journal · doi:10.1111/evj.12703 · Cited by 95 · see citing works
Pharmacokinetic/Pharmacodynamic Modelling in??Diabetes Mellitus
Landersdorfer, C. B., & Jusko, W. J. (2008) · Clinical Pharmacokinetics · doi:10.2165/00003088-200847070-00001 · Cited by 95 · see citing works
Kahn, S. E., Klaff, L. J., Schwartz, M. W., Beard, J. C., Bergman, R. N., Taborsky, G. J., & Porte, D. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-71-4-994 · Cited by 92 · see citing works
Pathogenesis of glucose intolerance in uremia
DeFronzo, R. A. (1978) · Metabolism · doi:10.1016/s0026-0495(78)80005-5 · Cited by 92 · see citing works
Gayet, C., Bailhache, E., Dumon, H., Martin, L., Siliart, B. S., & Nguyen, P. (2004) · Journal of Animal Physiology and Animal Nutrition · doi:10.1111/j.1439-0396.2003.00473.x · Cited by 90 · see citing works
The kinetics of insulin in man. I. General aspects
Ferrannini, E., & Cobelli, C. (1987) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610030201 · Cited by 90 · see citing works
Yang, Y. J., Hope, I. D., Ader, M., & Bergman, R. N. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.1.e17 · Cited by 90 · see citing works
How to measure insulin action in vivo
Scheen, A. J., Paquot, N., Castillo, M. J., & Lefèbvre, P. J. (1994) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610100206 · Cited by 89 · see citing works
Eggleston, E., Jahn, L. A., & Barrett, E. J. (2007) · Diabetes · doi:10.2337/db07-0670 · Cited by 89 · see citing works
“The potential importance of muscle perfusion for the delivery of insulin to muscle is underscored by studies demonstrating that in muscle, glucose metabolism correlates more strongly with interstitial than with plasma insulin levels (3; 4) and by considerable evidence that insulin’s trans-endothelial transport is rate…”
BackgroundThe endothelial cell: An “early responder” in the development of insulin resistance
Barrett, E. J., & Liu, Z. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-012-9232-6 · Cited by 88 · see citing works
“Support for this includes studies of whole body insulin kinetics that demonstrate a slow exchange of insulin between plasma and skeletal muscle which strongly correlates with insulin mediated glucose disposal as measured during the euglycemic insulin clamp procedure [62].”
Davis, S. N., Shavers, C., & Costa, F. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.279.5.e1054 · Cited by 86 · see citing works
The future of open- and closed-loop insulin delivery systems
Farmer, T. G., Edgar, T. F., & Peppas, N. A. (2007) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.60.1.0001 · Cited by 86 · see citing works
“Sherwin et al (1974) and Cerasi et al (1974) simultaneously developed a three-compartment pharmacokinetic model in which a central compartment is continuously exchanging insulin with two side compartments.”
BackgroundWhole body insulin resistance in myotonic dystrophy
Moxley, R. T., Corbett, A. J., Minaker, K. L., & Rowe, J. W. (1984) · Annals of Neurology · doi:10.1002/ana.410150208 · Cited by 85 · see citing works
Relationship between in Vivo Insulin Resistance and Decreased Insulin Receptors in Obese Man*
KOLTERMAN, O. G., REAVEN, G. M., & OLEFSKY, J. M. (1979) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-48-3-487 · Cited by 85 · see citing works
Meneilly, G. S., Elliott, T. G., Tessier, D., Hards, L., & Tildesley, H. D. (1996) · Diabetes Care · doi:10.2337/diacare.19.12.1320 · Cited by 84 · see citing works
“The volume of distribution of glucose was assumed to be 210 ml/kg (10).”
BackgroundRegulation of brittle diabetics by a pre-planned insulin infusion programme
Deckert, T., & L�rup, B. (1976) · Diabetologia · doi:10.1007/bf01220633 · Cited by 84 · see citing works
Hepatic disposal of biosynthetic human insulin and porcine C-peptide in humans
Bratusch-Marrain, P. R., Waldhäusl, W. K., Gasic, S., & Hofer, A. (1984) · Metabolism · doi:10.1016/0026-0495(84)90128-8 · Cited by 83 · see citing works
- Authors
- Sherwin, R. S., Kramer, K. J., Tobin, J. D., Insel, P. A., Liljenquist, J. E., Berman, M., & Andres, R.
- Affiliations
- National Institutes of Health (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1974-05-01
- Volume
- 53
- Issue
- 5
- Pages
- 1481-1492
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC302637
- OpenAlex
- W1969759774
- Cited by
- 460
- References
- 48
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 14 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 10 · 2015: 8 · 2014: 7 · 2013: 7 · 2012: 9
- FWCI
- 13.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- insulin kinetics, three-compartment model, porcine insulin, glucose clamp, glucose utilization, insulin half-life, inulin space
- MeSH terms
- Adolescent, Adult, Animals, Blood Glucose, Glucose, Half-Life, Humans, Insulin, Kinetics, Male, Middle Aged, Models, Biological, Swine
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