Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance.
Open accessAbstract
Obesity is characterized by decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Since IMGU equals the product of the arteriovenous glucose difference (AVGd) across muscle and blood flow into muscle, reduced blood flow and/or tissue activity (AVGd) can lead to decreased IMGU. To examine this issue, we studied six lean (weight 68 +/- 3 kg, mean +/- SEM) and six obese (94 +/- 3 kg) men. The insulin dose-response curves for whole body and leg IMGU were constructed using the euglycemic clamp and leg balance techniques over a large range of serum insulin concentrations. In lean and obese subjects, whole body IMGU, AVGd, blood flow, and leg IMGU increased in a dose dependent fashion and maximal rates of all parameters were reduced in obese subjects compared to lean subjects. The dose-response curves for whole body IMGU, leg IMGU, and AVGd were right-shifted in obese subjects with an ED50 two- to threefold higher than that of lean subjects for each parameter. Leg blood flow increased approximately twofold from basal 2.7 +/- 0.2 to 4.4 +/- 0.2 dl/min in lean, P less than 0.01, and from 2.5 +/- 0.3 to 4.4 +/- 0.4 dl/min in obese subjects, P less than 0.01. The ED50 for insulin's effect to increase leg blood flow was about fourfold higher for obese (957 pmol/liter) than lean subjects (266 pmol/liter), P less than 0.01. Therefore, decreased insulin sensitivity in human obesity is not only due to lower glucose extraction in insulin-sensitive tissues but also to lower blood flow to these tissues. Thus, in vivo insulin resistance can be due to a defect in insulin action at the tissue level and/or a defect in insulin's hemodynamic action to increase blood flow to insulin sensitive tissues.
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Stimulation of blood flow to insulin-sensitive tissues during insulin/glucose and glucose infusion may be an important determinant of the rate of in vivo glucose uptake.
“First, there is increasing evidence that stimulation of blood flow to insulin-sensitive tissues during insulin/glucose and glucose infusion may be an important determinant of the rate of in vivo glucose uptake (10, 11, 38).”
From Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) · cites this paper as [11]
The Discussion (page not provided) says increased blood flow is closely linked to glucose uptake and may contribute particularly after two hours of hyperinsulinemia. The Protocol describes insulin infusion with glucose clamped at euglycemia, but the paper does not establish the same point for glucose infusion without insulin. Its findings also concern skeletal muscle rather than insulin-sensitive tissues generally. (LLM, conf=0.85)
Experimental — accuracy not yet measuredInsulin-induced stimulation of blood flow to skeletal muscle is closely correlated with insulin-mediated muscle glucose uptake.
“More recently, evidence has accumulated in humans, indicating that insulin's cardiovascular effects may be involved in metabolic regulation (10, 11). Insulin-induced stimulation of blood flow to skeletal muscle, a major insulin-sensitive tissue, has been found to be closely correlated with insulin-mediated muscle glucose uptake.”
From Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) · cites this paper as [11]
Insulin resistance is associated with attenuated hyperinsulinemia-induced vasodilation in skeletal muscle.
“as recent evidence indicates that insulin resistance is associated with attenuated hyperinsulinemia-induced vasodilation in skeletal muscle (10, 11).”
From Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) · cites this paper as [11]
Insulin-induced increases in skeletal muscle blood flow play an important role in glucose delivery and uptake, and impaired insulin-induced vasodilation in skeletal muscle contributes importantly to reduced glucose uptake in skeletal muscle and to insulin resistance.
“Laakso et al83 introduced the concept that insulin-induced increases in skeletal muscle blood flow play an important role in glucose delivery and uptake, i.e. impaired insulin-induced vasodilation in skeletal muscle contributes importantly to reduced glucose uptake in skeletal muscle and to insulin resistance.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [83]
Insulin-induced vasodilation in skeletal muscle is reduced in obese, insulin resistant humans.
“Laakso et al83 reported that insulin-induced vasodilation in skeletal muscle is reduced in obese, insulin resistant humans.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [83]
Subjects who are insulin-resistant require less glucose at a fixed insulin dose than subjects with normal insulin sensitivity.
“Subjects who are insulin-resistant require less glucose at a fixed insulin dose than subjects with normal insulin sensitivity”
From The Vasculature in Prediabetes (2018) · cites this paper as [6]
Subjects with prediabetes require more glucose than a subject with overt type 2 diabetes mellitus during a glucose clamp.
“subjects with prediabetes require more glucose than a subject with overt type 2 diabetes mellitus (T2DM).”
From The Vasculature in Prediabetes (2018) · cites this paper as [6]
Insulin vasodilates skeletal muscle and coronary vasculature.
“Insulin vasodilates skeletal muscle6, 37 and coronary38, 39 vasculature.”
From The Vasculature in Prediabetes (2018) · cites this paper as [6]
Attenuated increases in insulin-stimulated limb blood flow result in decreased limb glucose uptake.
“Attenuated increases in insulin-stimulated limb blood flow result in decreased limb glucose uptake.”
From The Vasculature in Prediabetes (2018) · cites this paper as [6]
Studies with the euglycaemic clamp have yielded conflicting results in humans regarding blood flow: some reported increased blood flow in skeletal muscles of the limbs, whereas others reported unchanged blood flow.
“Studies with the euglycaemic clamp have yielded conflicting results in humans.A number of studies have reported an increased blood flow in skeletal muscles of the limbs [14,26,[34][35][36], whereas others have reported unchanged blood flow [37][38][39].”
From The sympathetic response to euglycaemic hyperinsulinaemia: Evidence from microelectrode nerve recordings in healthy subjects (1992) · cites this paper as [36]
A dose-response relationship between plasma insulin concentration and enhanced leg blood flow has been established, and insulin resistance is associated with a blunted vasodilatory response.
“Recently, a dose-response relationship between the plasma insulin concentration and enhanced leg blood flow has been established and insulin resistance was associated with a blunted vasodilatory response [36].”
From The sympathetic response to euglycaemic hyperinsulinaemia: Evidence from microelectrode nerve recordings in healthy subjects (1992) · cites this paper as [36]
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Cites
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
Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance.
National Diabetes Data Group (1979) · Diabetes · doi:10.2337/diab.28.12.1039 · Cited by 4,909 · see citing works
The Triumvirate: β-Cell, Muscle, Liver: A Collusion Responsible for NIDDM
DeFronzo, R. A. (1988) · Diabetes · doi:10.2337/diab.37.6.667 · Cited by 2,456 · see citing works
DeLÉAN, A., Munson, P. J., & Rodbard, D. (1978) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1978.235.2.e97 · Cited by 2,384 · see citing works
DeFronzo, R. A., Jacot, E., Jequier, E., Maeder, E., Wahren, J., & Felber, J. P. (1981) · Diabetes · doi:10.2337/diab.30.12.1000 · Cited by 1,770 · see citing works
Desbuquois, B., & Aurbach, G. D. (1971) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-33-5-732 · Cited by 1,301 · see citing works
Assessment 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
Lillioja, S., Young, A. A., Culter, C. L., Ivy, J. L., Abbott, W. G., Zawadzki, J. K., Yki-Järvinen, H., Christin, L., Secomb, T. W., & Bogardus, C. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113088 · Cited by 782 · see citing works
Colorimetric determination of free fatty acids in biological fluids
Itaya, K., & Ui, M. (1965) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39633-4 · Cited by 720 · 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
Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans
Baron, A., Brechtel, G., Wallace, P., & Edelman, S. V. (1988) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1988.255.6.e769 · Cited by 645 · see citing works
Self-citationFinegood, D. T., Bergman, R. N., & Vranić, M. (1987) · Diabetes · doi:10.2337/diab.36.8.914 · Cited by 546 · see citing works
ON THE HORMONAL REGULATION OF CARBOHYDRATE METABOLISM; STUDIES WITH C14 GLUCOSE.
DeBodo, R. C., Steele, R., ALTSZULER, N., Dunn, A., & Bishop, J. (1963) · PubMed · Cited by 532 · see citing works
Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man.
Gelfand, R. A., & Barrett, E. J. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113033 · Cited by 522 · see citing works
Rabinowitz, D. L., & Zierler, K. L. (1962) · Journal of Clinical Investigation · doi:10.1172/jci104676 · Cited by 521 · see citing works
Regulation of Splanchnic and Peripheral Glucose Uptake by Insulin and Hyperglycemia in Man
DeFronzo, R. A., Ferrannini, E., Hendler, R., Felig, P., & Wahren, J. (1983) · Diabetes · doi:10.2337/diab.32.1.35 · Cited by 509 · see citing works
Thiebaud, D., Jacot, E., Defronzo, R. A., Maeder, E., Jequier, E., & Felber, J.-P. (1982) · Diabetes · doi:10.2337/diacare.31.11.957 · Cited by 489 · see citing works
Johnson, P. C. (1986) · Circulation Research · doi:10.1161/01.res.59.5.483 · Cited by 414 · see citing works
Zierler, K. L. (1961) · Journal of Clinical Investigation · doi:10.1172/jci104437 · Cited by 403 · see citing works
Effect of exercise on insulin action in human skeletal muscle
Richter, E. A., Mikines, K. J., Galbo, H., & Kiens, B. (1989) · Journal of Applied Physiology · doi:10.1152/jappl.1989.66.2.876 · Cited by 357 · see citing works
Relationship between degree of obesity and in vivo insulin action in man
BOGARDUS, C., Lillioja, S., Mott, D. M., Hollenbeck, C. B., & Reaven, G. M. (1985) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1985.248.3.e286 · Cited by 343 · 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
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
Dohm, G. L., Tapscott, E. B., Pories, W. J., Dabbs, D. J., Flickinger, E. G., Meelheim, D., Fushiki, T., Atkinson, S., Elton, C. W., & Caro, J. F. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113622 · Cited by 297 · see citing works
Role of Lipid Oxidation in Pathogenesis of Insulin Resistance of Obesity and Type II Diabetes
Jp, F., Ferrannini, E., Golay, A., Meyer, H. U., Theibaud, D., Curchod, B., Maeder, E., Jéquier, E., & DeFronzo, R. A. (1987) · Diabetes · doi:10.2337/diab.36.11.1341 · Cited by 277 · see citing works
Insulin Infusion in Conscious Dogs
Liang, C., Doherty, J. U., FAILLACE, R. T., Maekawa, K., Arnold, S., Gavras, H. P., & Hood, W. B. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110572 · Cited by 277 · see citing works
Kinetics of glucose disposal in whole body and across the forearm in man.
Yki‐Järvinen, H., Young, A. A., Lamkin, C., & Foley, J. E. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113011 · Cited by 265 · see citing works
Effect of insulin on the distribution and disposition of glucose in man.
Ferrannini, E., Smith, J. D., Cobelli, C., Toffolo, G., Pilo, A., & DeFronzo, R. A. (1985) · Journal of Clinical Investigation · doi:10.1172/jci111969 · Cited by 254 · see citing works
Campbell, P. J., Mandarino, L. J., & Gerich, J. E. (1988) · Metabolism · doi:10.1016/0026-0495(88)90023-6 · Cited by 226 · 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
Evans, D. J., Murray, R., & Kissebah, A. H. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111565 · Cited by 201 · see citing works
Beta adrenergic-mediated vasodilator response to insulin in the human forearm.
Creager, M. A., Liang, C., & Coffman, J. D. (1985) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24198-2 · Cited by 192 · see citing works
Garvey, W. T., Huecksteadt, T. P., Matthaei, S., & Olefsky, J. M. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113485 · Cited by 169 · see citing works
Relationship between insulin-mediated glucose disposal and lipid metabolism in man.
Lillioja, S., Bogardus, C., Mott, D. M., Kennedy, A. L., Knowler, W. C., & Howard, B. V. (1985) · Journal of Clinical Investigation · doi:10.1172/jci111804 · Cited by 150 · see citing works
Forearm Glucose Uptake During the Oral Glucose Tolerance Test in Normal Subjects
Jackson, R. A., Peters, N., Advani, U., Perry, G., Rogers, J., Brough, W. H., & Pilkington, T. R. E. (1973) · Diabetes · doi:10.2337/diab.22.6.442 · Cited by 139 · see citing works
Jackson, R. A., Roshania, R. D., Hawa, M., Sim, B. M., & Disilvio, L. (1986) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jcem-63-3-541 · Cited by 128 · see citing works
Enhanced Glucose Utilization During Prolonged Glucose Clamp Studies
Doberne, L., Greenfield, M. S., Schulz, B., & Reaven, G. M. (1981) · Diabetes · doi:10.2337/diab.30.10.829 · Cited by 120 · see citing works
Kinetics of In Vivo Muscle Insulin-Mediated Glucose Uptake in Human Obesity
Laakso, M., Edelman, S. V., Olefsky, J. M., Brechtel, G., Wallace, P., & Baron, A. (1990) · Diabetes · doi:10.2337/diab.39.8.965 · Cited by 99 · see citing works
Self-citationFelber, J. P., Meyer, H. U., Curchod, B., Iselin, H. U., Rousselle, J., Maeder, E., Pahud, P., & Jéquier, E. (1981) · Diabetologia · doi:10.1007/bf00253814 · Cited by 95 · see citing works
Ciaraldi, T. P., Kolterman, O., & Olefsky, J. M. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110342 · Cited by 93 · see citing works
Importance of the Hematocrit in Interpretation of Blood Sugar
Dillon, R. S. (1965) · Diabetes · doi:10.2337/diab.14.10.672 · Cited by 89 · see citing works
Cellular mechanisms of insulin resistance in non-insulin-dependent (type II) diabetes
Olefsky, J. M., Garvey, W. T., Henry, R. R., Brillon, D. J., Matthael, S., & Freidenberg, G. R. (1988) · The American Journal of Medicine · doi:10.1016/0002-9343(88)90401-9 · Cited by 85 · see citing works
GANZ, V., Hlavová, A., Fronek, A. S., Linhart, J., & Přerovský, I. (1964) · Circulation · doi:10.1161/01.cir.30.1.86 · Cited by 69 · see citing works
Role of lipid oxidation in pathogenesis of insulin resistance of obesity and type II diabetes
Felber, J. P., Ferrannini, E., Golay, A., et al. (1987) · Diabetes · doi:10.2337/diabetes.36.11.1341 · Cited by 68 · see citing works
Heterogeneity of insulin action in muscle: influence of blood flow
James, D. E., Burleigh, K. M., Storlien, L. H., Bennett, S. P., & Kraegen, E. W. (1986) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1986.251.4.e422 · Cited by 66 · see citing works
Regulation of muscle blood flow
HUDLICKÁ, O. (1985) · Clinical Physiology · doi:10.1111/j.1365-2281.1985.tb00021.x · Cited by 63 · see citing works
Fisher, B. M., Gillen, G., Dargie, H. J., Inglis, G., & Frier, B. M. (1987) · Diabetologia · doi:10.1007/bf00274791 · Cited by 61 · see citing works
Jackson, R. A., Hamling, J., Blix, P., Sim, B. M., Hawa, M., Jaspan, J., Belin, J., & Nabarro, J. (1986) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jcem-63-3-594 · Cited by 49 · see citing works
Karnieli, E., Barzilai, A., Rafaeloff, R., & Armoni, M. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112660 · Cited by 44 · see citing works
Kinetics of in vivo muscle insulin-mediated glucose uptake in human obesity
Laakso, M., Edelman, S. V., Olefsky, J. M., et al. (1990) · Diabetes · doi:10.2337/diabetes.39.8.965 · Cited by 25 · see citing works
Self-citationFasting Decreases Rates of Noninsulin-Mediated Glucose Uptake in Man*
Baron, A., Brechtel, G., Wallace, P., & Edelman, S. V. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-67-3-532 · Cited by 15 · see citing works
Self-citationFelber, J. P., Meyer, H. U., Curchod, B., Iselin, H. U., Rousselle, J., Maeder, E., Pahud, P., & Jéquier, E. (1981) · Diabetologia · doi:10.1007/bf01789111 · Cited by 10 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Snyder, W. S., M. J. Cook, E. S. Nasset, L. R. Karhausen, G. P. Howells, and I. H. Tipton. 1974. Report ofthe task group on reference man. A report prepared by a task group of committee 2 ofthe interna- tional commission on regional protection. Pergamon Press Ltd., Ox- ford. p. 109.
Cited by
Sorted by citations
Steinberg, H. O., Chaker, H., Leaming, R., Johnson, A., Brechtel, G., & Baron, A. D. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118709 · Cited by 1,687 · see citing works
Self-citationCreager, M. A., Lüscher, T. F., of, P. W. T. A., Cosentino, F., & Beckman, J. A. (2003) · Circulation · doi:10.1161/01.cir.0000091257.27563.32 · Cited by 1,654 · see citing works
Kim, J.-A., Montagnani, M., Koh, K. K., & Quon, M. J. (2006) · Circulation · doi:10.1161/circulationaha.105.563213 · Cited by 1,652 · see citing works
Reaven, G. M., Lithell, H., & Landsberg, L. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602083340607 · Cited by 1,435 · see citing works
Insulin resistance and cardiovascular disease
Ginsberg, H. N. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10762 · Cited by 1,358 · see citing works
Steinberg, H. O., Brechtel, G., Johnson, A., Fineberg, N. S., & Baron, A. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117433 · Cited by 1,216 · see citing works
Self-citationHyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans.
Anderson, E. A., Hoffman, R. P., Balon, T. W., Sinkey, C. A., & Mark, A. L. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115260 · Cited by 1,075 · see citing works
Cardiovascular Actions of Insulin
Muniyappa, R., Montagnani, M., Koh, K. K., & Quon, M. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0006 · Cited by 873 · see citing works
Insulin resistance and hyperglycaemia in cardiovascular disease development
Laakso, M., & Kuusisto, J. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.29 · Cited by 862 · see citing works
Self-citationElevated circulating free fatty acid levels impair endothelium-dependent vasodilation
Steinberg, H. O., Tarshoby, M., Monestel, R., Hook, G., Cronin, J., Johnson, A., Bayazeed, B., & Baron, A. D. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119636 · Cited by 761 · see citing works
Self-citationNitric oxide release accounts for insulin's vascular effects in humans.
Scherrer, U., Randin, D., Vollenweider, P., Vollenweider, L., & NICOD, P. H. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117621 · Cited by 755 · see citing works
Zeng, G., & Quon, M. J. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118871 · Cited by 726 · see citing works
Role of Body Fat Distribution and the Metabolic Complications of Obesity
Jensen, M. D. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1585 · Cited by 691 · see citing works
Schalkwijk, C., & Stehouwer, C. D. A. (2019) · Physiological Reviews · doi:10.1152/physrev.00001.2019 · Cited by 630 · see citing works
The Sympathetic Nervous System Alterations in Human Hypertension
Grassi, G., Mark, A., & Esler, M. (2015) · Circulation Research · doi:10.1161/circresaha.116.303604 · Cited by 616 · see citing works
Hemodynamic actions of insulin
Baron, A. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.267.2.e187 · Cited by 608 · see citing works
Self-citationLehto, S., NISKANEN, L. K., Suhonen, M., Rönnemaa, T., & Laakso, M. (1996) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.16.8.978 · Cited by 595 · see citing works
Self-citationMahfoud, F., Schlaich, M. P., Kindermann, I., Ukena, C., Cremers, B., Brandt, M. C., Hoppe, U. C., Vonend, O., Rump, L. C., Sobotka, P. A., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.991869 · Cited by 572 · see citing works
Duplain, H., Burcelin, R., Sartori, C., Cook, S., Egli, M., Lepori, M., Vollenweider, P., Pedrazzini, T., Nicod, P., Thorens, B., et al. (2001) · Circulation · doi:10.1161/01.cir.104.3.342 · Cited by 533 · see citing works
Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases
Cersósimo, E., & DeFronzo, R. A. (2006) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.634 · Cited by 525 · see citing works
Diabetic Microvascular Disease: An Endocrine Society Scientific Statement
Barrett, E. J., Liu, Z., Khamaisi, M., King, G. L., Klein, R., Klein, R., Hughes, T. M., Craft, S., Freedman, B. I., Bowden, D. W., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01922 · Cited by 519 · see citing works
How to measure insulin sensitivity
Ferrannini, E., & Mari, A. (1998) · Journal of Hypertension · doi:10.1097/00004872-199816070-00001 · Cited by 506 · see citing works
The Insulin Resistance Atherosclerosis Study (IRAS)
Wagenknecht, L. E., Mayer, E. J., Rewers, M., Haffner, S. M., Selby, J. V., Borok, G. M., Henkin, L. F., Howard, G., Savage, P. J., Saad, M. F., et al. (1995) · Annals of Epidemiology · doi:10.1016/1047-2797(95)00062-3 · Cited by 493 · see citing works
Interaction between glucose and free fatty acid metabolism in human skeletal muscle.
Kelley, D. E., Mokáň, M., Simoneau, J. A., & Mandarino, L. J. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116603 · Cited by 481 · see citing works
The impact of insulin resistance on the kidney and vasculature
Artunç, F., Schleicher, E. D., Weigert, C., Fritsche, A., Stefan, N., & Häring, H. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.145 · Cited by 474 · see citing works
Balletshofer, B. M., Rittig, K., Enderle, M. D., Volk, A., Maerker, E., Jacob, S., Matthaei, S., Kristian, R. E. T. T., & Häring, H. U. (2000) · Circulation · doi:10.1161/01.cir.101.15.1780 · Cited by 437 · see citing works
de Jongh, R. T., Serné, E. H., IJzerman, R. G., de Vries, G., & Stehouwer, C. D. A. (2004) · Circulation · doi:10.1161/01.cir.0000129772.26647.6f · Cited by 407 · see citing works
The sympathetic nervous system and the metabolic syndrome
Mancia, G., Bousquet, P., Elghozi, J. L., Esler, M., Grassi, G., Julius, S., Reid, J., & Van Zwieten, P. A. (2007) · Journal of Hypertension · doi:10.1097/hjh.0b013e328048d004 · Cited by 385 · see citing works
Body fat and sympathetic nerve activity in healthy subjects.
Scherrer, U., Randin, D., Tappy, L., Vollenweider, P., Jéquier, E., & Nicod, P. (1994) · Circulation · doi:10.1161/01.cir.89.6.2634 · Cited by 383 · see citing works
Baron, A., Steinberg, H. O., Chaker, H., Leaming, R., Johnson, A., & Brechtel, G. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118124 · Cited by 380 · see citing works
Self-citationFree fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production.
Steinberg, H. O., Paradisi, G., Brechtel, G., Crowder, K., Cronin, J., & Baron, A. (2000) · Diabetes · doi:10.2337/diabetes.49.7.1231 · Cited by 380 · see citing works
Self-citationTissue–Specific Insulin Signaling, Metabolic Syndrome, and Cardiovascular Disease
Rask‐Madsen, C., & Kahn, C. R. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.241919 · Cited by 376 · see citing works
Scherrer, U., & Sartori, C. (1997) · Circulation · doi:10.1161/01.cir.96.11.4104 · Cited by 371 · see citing works
Diabetes mellitus, hypertension, and cardiovascular disease: Which role for oxidative stress?
Giugliano, D., Ceriello, A., & Paolisso, G. (1995) · Metabolism · doi:10.1016/0026-0495(95)90167-1 · Cited by 369 · see citing works
Skeletal muscle blood flow. A possible link between insulin resistance and blood pressure.
Baron, A., Brechtel, G., Johnson, A., & Hardin, D. S. (1993) · Hypertension · doi:10.1161/01.hyp.21.2.129 · Cited by 366 · see citing works
Self-citationBlood 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
Lambert, G. W., Straznicky, N. E., Lambert, É., Dixon, J. B., & Schlaich, M. P. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.02.002 · Cited by 345 · see citing works
Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes.
Boden, G., & Chen, X. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118160 · Cited by 344 · see citing works
Vascular function, insulin resistance and fatty acids
Steinberg, H. O., & Baron, A. (2002) · Diabetologia · doi:10.1007/s00125-002-0800-2 · Cited by 339 · see citing works
Self-citationObesity and Body Fat Distribution Induce Endothelial Dysfunction by Oxidative Stress
Perticone, F., Ceravolo, R., Candigliota, M., Ventura, G., Iacopino, S., Sinopoli, F., & Mattioli, P. L. (2001) · Diabetes · doi:10.2337/diabetes.50.1.159 · Cited by 336 · see citing works
Insulin: The master regulator of glucose metabolism
Norton, L., Shannon, C. E., Gastaldelli, A., & DeFronzo, R. A. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155142 · Cited by 337 · see citing works
The Treatment of Hypertension in Adult Patients With Diabetes
Arauz-Pacheco, C., Parrott, M. A., & Raskin, P. (2002) · Diabetes Care · doi:10.2337/diacare.25.1.134 · Cited by 326 · see citing works
Rothman, D. L., Magnusson, I., Cline, G., Gerard, D., Kahn, C. R., Shulman, R. G., & Shulman, G. I. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.4.983 · Cited by 325 · see citing works
Rothman, D. L., Shulman, R. G., & Shulman, G. I. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115686 · Cited by 328 · see citing works
Retinal arteriolar narrowing and risk of diabetes mellitus in middle-aged persons
Wong, T. Y. (2002) · JAMA · doi:10.1001/jama.287.19.2528 · Cited by 320 · see citing works
Barrett, 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
Vollenweider, P., Tappy, L., Randin, D., Schneiter, P., Jéquier, E., Nicod, P., & Scherrer, U. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116542 · Cited by 321 · see citing works
Reflex sympathetic activation induces acute insulin resistance in the human forearm.
Jamerson, K. A., Julius, S., Gudbrandsson, T., Andersson, O., & Brant, D. O. (1993) · Hypertension · doi:10.1161/01.hyp.21.5.618 · Cited by 311 · see citing works
Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences
Stehouwer, C. D. A. (2018) · Diabetes · doi:10.2337/dbi17-0044 · Cited by 304 · see citing works
Insulin Stimulates Both Endothelin and Nitric Oxide Activity in the Human Forearm
Cardillo, C., Nambi, S. S., Kilcoyne, C. M., Choucair, W. K., Katz, A., Quon, M. J., & Panza, J. A. (1999) · Circulation · doi:10.1161/01.cir.100.8.820 · Cited by 301 · see citing works
Cardiovascular Disease in Type 2 Diabetes From Population to Man to Mechanisms
Laakso, M. (2010) · Diabetes Care · doi:10.2337/dc09-0749 · Cited by 299 · see citing works
Self-citationObesity Blunts Insulin-Mediated Microvascular Recruitment in Human Forearm Muscle
Clerk, L. H., Keske, M. A., Jahn, L. A., Liu, Z., Lindner, J. R., & Barrett, E. J. (2006) · Diabetes · doi:10.2337/db05-1373 · Cited by 300 · see citing works
Oxidative stress and insulin action: is there a relationship?
Paolisso, G., & Giugliano, D. (1996) · Diabetologia · doi:10.1007/bf00418354 · Cited by 294 · see citing works
Berne, C., Fagius, J., Pollare, T., & Hjemdahl, P. (1992) · Diabetologia · doi:10.1007/bf00399935 · Cited by 293 · see citing works
Vollenweider, P., Randin, D., Tappy, L., Jéquier, E., Nicod, P., & Scherrer, U. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117242 · Cited by 285 · see citing works
Wong, T. Y., Duncan, B. B., Golden, S. H., Klein, R., Couper, D. J., Klein, B. E. K., Hubbard, L. D., Sharrett, A. R., & Schmidt, M. I. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-0069 · Cited by 281 · see citing works
Jonk, A. M., Houben, A. J. H. M., de Jongh, R. T., Serné, E. H., Schaper, N. C., & Stehouwer, C. D. A. (2007) · Physiology · doi:10.1152/physiol.00012.2007 · Cited by 279 · see citing works
Insulin-induced vasodilatation: physiology or pharmacology?
Yki‐Järvinen, H., & Utriainen, T. (1998) · Diabetologia · doi:10.1007/s001250050919 · Cited by 260 · see citing works
Physiologic Hyperinsulinemia Enhances Human Skeletal Muscle Perfusion by Capillary Recruitment
Coggins, M. P., Lindner, J. R., Rattigan, S., Jahn, L. A., Fasy, E. A., Kaul, S., & Barrett, E. J. (2001) · Diabetes · doi:10.2337/diabetes.50.12.2682 · Cited by 260 · see citing works
Shinozaki, K., Nishio, Y., Okamura, T., Yoshida, Y., Maegawa, H., Kojima, H., Masada, M., Toda, N., Kikkawa, R., & Kashiwagi, A. (2000) · Circulation Research · doi:10.1161/01.res.87.7.566 · Cited by 242 · see citing works
The vasodilator action of insulin. Implications for the insulin hypothesis of hypertension.
Anderson, E. A., & Mark, A. L. (1993) · Hypertension · doi:10.1161/01.hyp.21.2.136 · Cited by 242 · see citing works
Williams, I. L., Wheatcroft, S. B., Shah, A. M., & Kearney, M. T. (2002) · International Journal of Obesity · doi:10.1038/sj.ijo.0801995 · Cited by 261 · see citing works
Blood pressure lowering by pioglitazone. Evidence for a direct vascular effect.
Buchanan, T. A., Meehan, W. P., Jeng, Y. Y., Yang, D. T., Chan, T. M., Nadler, J. L., Scott, S., Rude, R. K., & Hsueh, W. A. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118041 · Cited by 238 · see citing works
Ayala, J. E., Bracy, D. P., Julien, B. M., Rottman, J. N., Fueger, P. T., & Wasserman, D. H. (2007) · Diabetes · doi:10.2337/db06-0883 · Cited by 237 · see citing works
Diabetes mellitus: A disease of abnormal cellular calcium metabolism?
Levy, J., Gavin, J. R., & Sowers, J. R. (1994) · The American Journal of Medicine · doi:10.1016/0002-9343(94)90152-x · Cited by 236 · see citing works
Ebeling, P. R., Bourey, R. E., Koranyi, L. I., Tuominen, J. A., Groop, L., Henriksson, J., Mueckler, M. M., Sovijärvi, A. R. A., & Koivisto, V. A. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116747 · Cited by 233 · see citing works
Donati, G., Stagni, B., Piscaglia, F., Venturoli, N., Morselli‐Labate, A. M., Rasciti, L., & Bolondi, L. (2004) · Gut · doi:10.1136/gut.2003.027086 · Cited by 231 · see citing works
Kelley, D. E., Mintun, M. A., Watkins, S. C., Simoneau, J. A., Jadali, F., Fredrickson, A., Beattie, J., & Thériault, R. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118724 · Cited by 228 · see citing works
PPARα deficiency reduces insulin resistance and atherosclerosis in apoE-null mice
Tordjman, K. M., Bernal‐Mizrachi, C., Zemany, L., Weng, S., Chu, F., Zhang, F., Leone, T. C., Coleman, T., Kelly, D. P., & Semenkovich, C. F. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11497 · Cited by 228 · see citing works
Insulin increases sympathetic activity but not blood pressure in borderline hypertensive humans.
Anderson, E. A., Balon, T. W., Hoffman, R. P., Sinkey, C. A., & Mark, A. L. (1992) · Hypertension · doi:10.1161/01.hyp.19.6.621 · Cited by 220 · see citing works
Insulin and Insulin Receptors in Adipose Tissue Development
Cignarelli, A., Genchi, V. A., Perrini, S., Natalicchio, A., Laviola, L., & Giorgino, F. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030759 · Cited by 222 · see citing works
Vincent, M. A., Dawson, D. K., Clark, A. D. H., Lindner, J. R., Rattigan, S., Clark, M. G., & Barrett, E. J. (2002) · Diabetes · doi:10.2337/diabetes.51.1.42 · Cited by 216 · see citing works
Whole body glucose metabolism.
Zierler, K. (1999) · American Journal of Physiology · doi:10.1152/ajpendo.1999.276.3.e409 · Cited by 219 · see citing works
Baron, A., Laakso, M., Brechtel, G., & Edelman, S. V. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-73-3-637 · Cited by 210 · see citing works
Self-citationCatecholamine-induced lipolysis in adipose tissue and skeletal muscle in obesity
Jocken, J. W. E., & Blaak, E. E. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.01.002 · Cited by 211 · see citing works
Exercise training improves baroreflex sensitivity in type 2 diabetes
Loimaala, A., Huikuri, H. V., Kööbi, T., Rinne, M., Nenonen, A., & Vuori, I. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1837 · Cited by 207 · see citing works
The sweeter side of ACE2: Physiological evidence for a role in diabetes
Bindom, S. M., & Lazartigues, E. D. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.09.020 · Cited by 212 · see citing works
Exercise Training Improves Vascular Endothelial Function in Patients with Type 1 Diabetes
Fuchsjäger‐Mayrl, G., Pleiner, J., Wiesinger, G., Sieder, A. E., Quittan, M., Nuhr, M. J., Francesconi, C. M., Hp, S., Francesconi, M., Schmetterer, L. F., et al. (2002) · Diabetes Care · doi:10.2337/diacare.25.10.1795 · Cited by 210 · see citing works
Mudaliar, S. R. D., Chang, A. R., & Henry, R. R. (2003) · Endocrine Practice · doi:10.4158/ep.9.5.406 · Cited by 209 · see citing works
Asymptomatic atherosclerosis and insulin resistance.
Laakso, M., Sarlund, H., Salonen, R. M., Suhonen, M., Pyörälà, K., Salonen, J. T., & Karhapää, P. (1991) · Arteriosclerosis and Thrombosis A Journal of Vascular Biology · doi:10.1161/01.atv.11.4.1068 · Cited by 206 · see citing works
Self-citationEndothelial dysfunction in insulin resistance and type 2 diabetes
Jansson, P. (2007) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01830.x · Cited by 201 · see citing works
Jacob, S., Kristian, R. E. T. T., & HENRIKSEN, E. (1998) · American Journal of Hypertension · doi:10.1016/s0895-7061(98)00141-1 · Cited by 204 · see citing works
Currie, C. J., Poole, C. D., Evans, M., Peters, J. R., & Morgan, C. L. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3042 · Cited by 203 · see citing works
Mixed meal and light exercise each recruit muscle capillaries in healthy humans
Keske, M. A., Clerk, L. H., Lindner, J. R., Price, W. J., Jahn, L. A., Leong-Poi, H. M., & Barrett, E. J. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00497.2005 · Cited by 201 · see citing works
Hunter, S. J., & Garvey, W. T. (1998) · The American Journal of Medicine · doi:10.1016/s0002-9343(98)00300-3 · Cited by 200 · see citing works
Insulin signaling in the arterial wall
Hsueh, W. A., & Law, R. E. (1999) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)00353-7 · Cited by 200 · see citing works
Clustering of cardiovascular risk factors in confirmed prehypertensive individuals.
Haffner, S. M., Ferrannini, E., Hazuda, H. P., & D, M. P. S. M. (1992) · Hypertension · doi:10.1161/01.hyp.20.1.38 · Cited by 195 · see citing works
Glycerol production in subcutaneous adipose tissue in lean and obese humans.
Jansson, P., Larsson, A., Smith, U., & Lönnroth, P. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115756 · Cited by 196 · see citing works
Skeletal muscle blood flow independently modulates insulin-mediated glucose uptake
Baron, A., Steinberg, H. O., Brechtel, G., & Johnson, A. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.2.e248 · Cited by 198 · see citing works
Self-citationEndothelial Dysfunction, Obesity and Insulin Resistance
Prieto, D., Contreras, C., & Sánchez, A. (2014) · Current Vascular Pharmacology · doi:10.2174/1570161112666140423221008 · Cited by 190 · see citing works
Insulin and Insulin-Like Growth Factor in Normal and Pathological Cardiovascular Physiology
Sowers, J. R. (1997) · Hypertension · doi:10.1161/01.hyp.29.3.691 · Cited by 184 · see citing works
The Search for Safer Glucocorticoid Receptor Ligands
Rosen, J., & Miner, J. N. (2005) · Endocrine Reviews · doi:10.1210/er.2005-0002 · Cited by 184 · see citing works
Maggs, D. G., Jacob, R. J., Rife, F., Lange, R., Leone, P., During, M. J., Tamborlane, W. V., & Sherwin, R. S. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118043 · Cited by 183 · see citing works
Overweight, physical activity and high blood pressure in children: a review of the literature.
Torrance, B. D., McGuire, K. A., Lewanczuk, R. Z., & McGavock, J. (2007) · PubMed Central · Cited by 181 · see citing works
Insulin differentially regulates systemic and skeletal muscle vascular resistance
Baron, A., & Brechtel, G. (1993) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1993.265.1.e61 · Cited by 180 · see citing works
Self-citationEffect of Endothelium-Specific Insulin Resistance on Endothelial Function In Vivo
Duncan, E. R., Crossey, P. A., Walker, S., Anilkumar, N. P., Poston, L., Douglas, G., Ezzat, V., Wheatcroft, S. B., Shah, A. M., & Kearney, M. T. (2008) · Diabetes · doi:10.2337/db07-1111 · Cited by 179 · see citing works
Proatherosclerotic Mechanisms Involving Protein Kinase C in Diabetes and Insulin Resistance
Rask‐Madsen, C., & King, G. L. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000155325.41507.e0 · Cited by 176 · see citing works
Tack, C. J. J., Ong, M. K. E., Lutterman, J. A., & Smits, P. (1998) · Diabetologia · doi:10.1007/s001250050948 · Cited by 177 · see citing works
Del Prato, S., Bonadonna, R. C., Bonora, E., Gulli, G., Solini, A., Shank, M., & DeFronzo, R. A. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116226 · Cited by 170 · see citing works
Endothelial dysfunction in metabolic syndrome: Prevalence, pathogenesis and management
Τζιόμαλος, Κ., Athyros, V. G., Karagiannis, A. I., & Mikhailidis, D. P. (2009) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2009.08.006 · Cited by 177 · see citing works
- Authors
- Laakso, M., Edelman, S. V., Brechtel, G., & Baron, A. D.
- Affiliations
- United States Department of Veterans Affairs (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1990-06-01
- Volume
- 85
- Issue
- 6
- Pages
- 1844-1852
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC296649
- OpenAlex
- W2164471793
- Cited by
- 930
- References
- 52
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 15 · 2021: 3 · 2020: 9 · 2019: 16 · 2018: 13 · 2017: 14 · 2016: 22 · 2015: 27 · 2014: 18 · 2013: 28 · 2012: 24
- FWCI
- 25.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (1f05tw003969-01)
- Fogarty International Center (TW 03969-01)
- National Center for Research Resources (MO1 RR00827, M01RR000827)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- insulin resistance, obesity, skeletal muscle blood flow, insulin-stimulated glucose uptake, arteriovenous glucose difference, leg blood flow, insulin dose-response, euglycemic clamp, insulin sensitivity
- MeSH terms
- Adult, Biological Transport, Fatty Acids, Nonesterified, Glucose, Humans, Insulin, Insulin Resistance, Lactates, Leg, Muscles, Obesity, Regional Blood Flow, Regression Analysis
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