Impaired Insulin-Mediated Skeletal Muscle Blood Flow in Patients With NIDDM
Abstract
Patients with non-insulin-dependent diabetes metlitus (NIDDM) exhibit decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Because IMGU is equal to the product of the arteriovenous glucose difference (AVGΔ) across and blood flow (F) into muscle (IMGU = AVGΔ × F), reduced tissue permeability (AVGΔ) and/or glucose and insulin delivery (F) can potentially lead to decreased IMGU. The components of skeletal muscle IMGU were studied in six obese NIDDM subjects (103 ± 9 kg) and compared with those previously determined in six lean (weight 68 ± 3 kg), and six obese (94 ± 3 kg) with normal glucose tolerance. The insulin dose-response curves for whole body and leg muscle IMGU were constructed using the combined euglycemic clamp and leg balance techniques during sequential insulin infusions (range of serum insulin 130–80,000 pmol/L). In lean, obese, and NIDDM subjects, whole body IMGU, femoral AVGΔ, and leg IMGU increased in a dose-dependent fashion over the range of insulin with an ED50 of 400–500 pmol/L in lean, 1000–1200 pmol/L in obese, and 4000–7000 pmol/L in NIDDM subjects (P < 0.01 lean vs. obese and NIDDM). In lean and obese subjects, maximally effective insulin concentrations increased leg blood flow ∼2-fold from basal with an ED50 of 266 pmol/L and 957 pmol/L, respectively (P < 0.01 lean vs. obese). In contrast, leg F did not increase from the basal value in NIDDM subjects (2.7 ± 0.1 vs. 3.5 ± 0.5 dl/min, NS). In the physiological range of insulin concentrations NIDDM subjects had lower body IMGU, leg F, femoral AVGΔ, and leg IMGU than obese and lean subjects, but at maximally effective insulin concentrations, femoral AVGA did not differ between obese and NIDDM subjects. Thus, 1) both reduced skeletal muscle tissue permeability and blood flow are found in NIDDM subjects and 2) impaired insulin-mediated augmentation of skeletal muscle blood flow in obese NIDDM patients is due to the diabetic state per se and not to the obesity status. Whether reduced skeletal muscle blood flow is the result or the cause of insulin resistance in patients with NIDDM remains to be elucidated.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [7]
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 [7]
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
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
Steinberg, H. O., Brechtel, G., Johnson, A., Fineberg, N. S., & Baron, A. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117433 · Cited by 1,219 · see citing works
“Moreover, we have previously established that insulin's ability to increase LBF is directly related to the degree of insulin sensitivity and is inversely related to obesity (1, 11).”
BackgroundSelf-citationCardiovascular Actions of Insulin
Muniyappa, R., Montagnani, M., Koh, K. K., & Quon, M. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0006 · Cited by 872 · see citing works
“Infusion of the competitive NOS inhibitor, N (G)-nitro-l-arginine methyl ester, completely blocks the effect of insulin to increase flow and partially blocks insulin-stimulated leg glucose uptake (134, 136).”
BackgroundElevated 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
“Interestingly, this insulin effect is either blunted or absent in obese insulin-resistant subjects with or without non-insulin-dependent diabetes mellitus (NIDDM) 1 (1, 3).”
BackgroundSelf-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
“A defect in insulin-induced stimulation of NOrelease could be one of the factors that contributes to altered vascular function (9, 21, 23) and hypertension (1) in insulin-resistant states.”
BackgroundZeng, G., & Quon, M. J. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118871 · Cited by 726 · see citing works
Regulatory role for the arginine–nitric oxide pathway in metabolism of energy substrates
Jobgen, W. S., Fried, S. K., Fu, W. J., Meininger, C. J., & Wu, G. (2006) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2005.12.001 · Cited by 713 · 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-citationDiabetic 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
“By the mid-1990s, it was reasonably 1688 established that changes in insulin concentration (using the insulin clamp technique) could 1689 modify total blood flow to muscle, and that states of insulin resistance [including obesity (415), 1690 T1DM (416), and T2DM (417)] blunted this effect.”
BackgroundVolpi, E., Mittendorfer, B., Rasmussen, B. B., & Wolfe, R. R. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.12.7021 · Cited by 464 · see citing works
“This may reflect a general response of insulin resistance, because previous studies have reported a similar alteration in the response of blood flow to insulin in type 2 diabetes patients (40, 41).”
ResultZierath, J. R., He, L., Gumà, A., Wahlström, E. O., Klip, A., & Wallberg-Henriksson, H. (1996) · Diabetologia · doi:10.1007/bf02658504 · Cited by 402 · see citing works
Bauman, W. A., & Spungen, A. M. (1994) · Metabolism · doi:10.1016/0026-0495(94)90126-0 · Cited by 405 · 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-citationScherrer, 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
Ivy, J. L. (1997) · Sports Medicine · doi:10.2165/00007256-199724050-00004 · Cited by 366 · see citing works
Blood 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
“(94)] constructed dose-response curves for insulin-mediated increases in femoral blood flow and leg glucose uptake in healthy, obese, and obese type 2 diabetic subjects.”
BackgroundInfluentialVascular 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
“The results of a series of studies have indicated that insulin-resistant subjects with Type II diabetes had severely impaired increments in LBF [50].”
BackgroundSelf-citationRetinal 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
“Indeed, they showed a remarkable correlation between the effect of insulin on whole body glucose uptake and the effect of insulin on leg blood flow over a broad range of insulin sensitivities in normal and insulin-resistant states [30-32].”
BackgroundInsulin 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
“We demonstrated that insulin-stimulated increase in leg glucose disposal and blood flow were coupled in a dose-dependent manner (23,24).”
BackgroundSelf-citationVollenweider, 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
Antioxidants, diabetes and endothelial dysfunction
Laight, D. W. (2000) · Cardiovascular Research · doi:10.1016/s0008-6363(00)00054-7 · Cited by 264 · 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
Fujita, S., Rasmussen, B. B., Cadenas, J. G., Grady, J. J., & Volpi, E. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00271.2005 · Cited by 264 · see citing works
“This may be an important issue in certain conditions such as diabetes or aging, since amino acid delivery may not increase during hyperinsulinemia due to a decreased vasodilatory response to insulin (26, 30, 44, 51).”
BackgroundPhysiologic 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
“Yet, even when similar thermodilution methods were used, findings supporting (43) or denying (11) a defect in insulin-induced flow enhancement have been reported.”
MethodThe 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
Keske, M. A., Montagnani, M., & Quon, M. J. (2003) · Current Diabetes Reports · doi:10.1007/s11892-003-0018-9 · Cited by 226 · see citing works
“Laakso et al. [ 52 ] showed that insulin sensitivity with respect to leg blood flow in humans is positively correlated with insulin sensitivity with respect to glucose disposal.”
BackgroundCameron, N. E., & Cotter, M. A. (1994) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610100302 · Cited by 224 · see citing works
Pathogenesis of non-insulin-dependent diabetes mellitus
Yki‐Järvinen, H. (1994) · The Lancet · doi:10.1016/s0140-6736(94)90821-4 · Cited by 227 · 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
“resistant disease states, such as type 2 diabetes, hypertension, and obesity, is reported to be blunted (1,4,26,27), providing further evidence that the hemodynamic involvement of insulin may be important for its action.”
BackgroundHuggett, R. J., Burns, J., Mackintosh, A. F., & Mary, D. A. S. G. (2004) · Hypertension · doi:10.1161/01.hyp.0000147893.08533.d8 · Cited by 211 · 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
Piatti, P., Monti, L. D., Valsecchi, G., Magni, F., Setola, E., Marchesi, F., Galli-Kienle, M., Pozza, G., & Alberti, K. G. M. M. (2001) · Diabetes Care · doi:10.2337/diacare.24.5.875 · Cited by 208 · see citing works
“In addition, in obese patients and patients with type 2 diabetes, the insulin-mediated vasodilatory response seems blunted (4).”
BackgroundInsulin 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
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
“The insulin clamp method has been extensively used to probe the vascular actions of insulin (2, 16, 17).”
MethodSkeletal 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-citationNitric oxide and vascular insulin resistance
Wu, G., & Meininger, C. J. (2009) · BioFactors · doi:10.1002/biof.3 · Cited by 190 · see citing works
“Conversely, an inhibition of NO production by NMMA blocks the insulin-induced increase in tissue blood flows and glucose uptake [6].”
Nitric Oxide Synthesis Is Reduced in Subjects With Type 2 Diabetes and Nephropathy
Tessari, P., Cecchet, D., Cosma, A., Vettore, M., Coracina, A., Millioni, R., Iori, E., Puricelli, L., Avogaro, A., & Vedovato, M. (2010) · Diabetes · doi:10.2337/db09-1772 · Cited by 187 · see citing works
“T2DM, type 2 diabetic subjects.”
InfluentialInsulin 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
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
Effect 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
“It has been suggested that endothelial cell IR might promote global metabolic IR secondary to decreased insulinstimulated blood flow to insulin sensitive tissues (27-29).”
Chen, H., Karne, R. J., Hall, G., Campia, U., Panza, J. A., Cannon, R. O., Wang, Y., Katz, A., Levine, M., & Quon, M. J. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00768.2005 · Cited by 178 · 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
Endothelial function is impaired in fit young adults of low birth weight
Goodfellow, J. (1998) · Cardiovascular Research · doi:10.1016/s0008-6363(98)00197-7 · Cited by 175 · see citing works
Baron, A., Tarshoby, M., Brechtel, G., Lazaridis, E. N., Cronin, J., Johnson, A., & Steinberg, H. O. (2000) · Diabetes · doi:10.2337/diabetes.49.5.768 · Cited by 174 · see citing works
“Better understanding of the underlying mechanism is an important issue, because insulin’s effect to stimulate skeletal muscle perfusion is diminished in states of insulin resistance (8,9) and, thus, it is possible that diminished tissue perfusion could contribute to insulin resistance in these subjects.”
BackgroundSelf-citationInsulin 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
“Most significantly, obesity (55) and type 1 (5) and type 2 diabetes (21, 56) appeared to proportionately diminish insulin-mediated blood flow and glucose disposal in the leg.”
BackgroundCurrent concepts in insulin resistance, type 2 diabetes mellitus, and the metabolic syndrome
Reusch, J. E. B. (2002) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)02555-9 · Cited by 167 · see citing works
Hällsten, K., Virtanen, K. A., Lönnqvist, F., Sipilä, H. T., Oksanen, A., Viljanen, T., Rönnemaa, T., Viikari, J. S. A., Knuuti, J. M., & Nuutila, P. (2002) · Diabetes · doi:10.2337/diabetes.51.12.3479 · Cited by 165 · see citing works
“Leg blood flow response to insulin is blunted in obesity and type 2 diabetes (54,55).”
BackgroundCardiovascular risk continuum: implications of insulin resistance and diabetes
Hsueh, W. A., & Law, R. E. (1998) · The American Journal of Medicine · doi:10.1016/s0002-9343(98)00205-8 · Cited by 158 · see citing works
Insulin resistance and vascular function
Baron, A. (2002) · Journal of Diabetes and its Complications · doi:10.1016/s1056-8727(01)00209-4 · Cited by 159 · see citing works
Self-citationThe vascular effects of L-Arginine in humans. The role of endogenous insulin.
Giugliano, D., Marfella, R., Verrazzo, G., Acampora, R., Coppola, L., Cozzolino, D., & D'Onofrio, F. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119177 · Cited by 159 · see citing works
“If l-arginine acts by stimulating NO synthesis, through the mediation of insulin or via some other still unidentified mechanisms, it may be an easy and simple tool to assess endotheliumdependent vascular function in pathophysiological conditions, including states of insulin resistance where the ability of insulin to m…”
BackgroundControl of Vascular Cell Proliferation and Migration by PPAR-γ
Hsueh, W. A., Jackson, S. M., & Law, R. E. (2001) · Diabetes Care · doi:10.2337/diacare.24.2.392 · Cited by 158 · see citing works
ROLE OF BLOOD FLOW IN THE REGULATION OF MUSCLEGLUCOSE UPTAKE
Baron, A., & Clark, M. G. (1997) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.17.1.487 · Cited by 156 · see citing works
Self-citationNuutila, P., Raitakari, M., Laine, H. K., Kirvelä, O., Takala, T., Utriainen, T., Mäkimattila, S., Pitkänen, O., Ruotsalainen, U., Iida, H., et al. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118601 · Cited by 157 · see citing works
Utriainen, T., Malmstr�m, R., ̈kimattila, S. M., & Yki-J�rvinen, H. (1995) · Diabetologia · doi:10.1007/bf00400724 · Cited by 158 · see citing works
“[3] have demonstrated that insulin induces a variety of haemodynamic responses in normal subjects and that deficiency of such responses to insulin characterizes several insulin-resistant states [2, 4, 5].”
BackgroundThe physiological regulation of glucose flux into musclein vivo
Wasserman, D. H., Kang, L., Ayala, J. E., Fueger, P. T., & Lee, R. S. (2010) · Journal of Experimental Biology · doi:10.1242/jeb.048041 · Cited by 150 · see citing works
“…state Insulin resistance can be associated with deficits in muscle blood flow (Clerk et al., 2007; Duplain et al., 2001; Inyard et al., 2009; Laakso et al., 1992), membrane glucose transport (Han et al., 1995; Liu et al., 1996; Zierath et al., 1997) and intracellular capacity to…”
BackgroundLamport, D. J., Lawton, C. L., Mansfield, M. W., & Dye, L. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.10.008 · Cited by 150 · see citing works
“However, it has been shown that type 2 diabetes and insulin resistance are characterised by abnormalities in endothelial vasodilatation (Baron, 1996; Cohen, 1993; Laakso et al., 1992; McVeigh et al., 1992).”
Retinal Arteriolar Narrowing, Hypertension, and Subsequent Risk of Diabetes Mellitus
Wong, T. Y. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.9.1060 · Cited by 150 · see citing works
Li, G., Barrett, E. J., Wang, H., Chai, W., & Liu, Z. (2005) · Endocrinology · doi:10.1210/en.2005-0505 · Cited by 149 · see citing works
Bonadonna, R. C., Saccomani, M. P., Prato, S. D., Bonora, E., DeFronzo, R. A., & Cobelli, C. (1998) · Circulation · doi:10.1161/01.cir.98.3.234 · Cited by 144 · see citing works
Richards, O. C., Raines, S. M., & Attie, A. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0035 · Cited by 141 · see citing works
The Vasculature in Prediabetes
Wasserman, D. H., Wang, T. J., & Brown, N. J. (2018) · Circulation Research · doi:10.1161/circresaha.118.311912 · Cited by 137 · see citing works
“Attenuated increases in insulin-stimulated limb blood flow result in decreased limb glucose uptake.(6,7) Indeed, rats and mice made insulinresistant by high fat intake have such severe impairment of microvascular blood flow that the delivery of glucose to skeletal muscle limits insulin-stimulated glucose uptake during…”
BackgroundAcute noradrenergic activation induces insulin resistance in human skeletal muscle
Lembo, G., Capaldo, B., Rendina, V., Iaccarino, G., Napoli, R., Guida, R., Trimarco, B., & Sacca, L. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.2.e242 · Cited by 136 · see citing works
Insulin: new roles for an ancient hormone
Ferrannini, Galvan, Gastaldelli, Camastra, Sironi, Toschi, Baldi, Frascerra, Monzani, Antonelli, et al. (1999) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1999.00536.x · Cited by 133 · see citing works
Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency.
Lembo, G., Rockman, H. A., Hunter, J. J., Steinmetz, H., Koch, W. J., Ma, L., Prinz, M. P., Ross, J., Chien, K. R., & Powell-Braxton, L. (1996) · Journal of Clinical Investigation · doi:10.1172/jci119086 · Cited by 132 · see citing works
Limberg, J. K., Casey, D. P., Trinity, J. D., Nicholson, W. T., Wray, D. W., Tschakovsky, M. E., GREEN, D. J., Hellsten, Y., Fadel, P. J., Joyner, M. J., et al. (2019) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00649.2019 · Cited by 130 · see citing works
“Furthermore, given that skeletal muscle resistance vessel function is positively associated with exercise tolerance and fitness (1, 54, 138, 173), blood pressure control (147, 199, 200), glucose homeostasis (12, 146), and lower cardiovascular risk (4, 109, 119, 172), improved vasomotor function in skeletal muscle resi…”
BackgroundInsulin Action in the Vasculature: Physiology and Pathophysiology
Mather, K. J., Anderson, T. J., & Verma, S. (2001) · Journal of Vascular Research · doi:10.1159/000051074 · Cited by 123 · see citing works
“demonstrated classical dose-response curves for blood flow responses in the leg to increasing concentrations of infused insulin. Importantly, differences in the sensitivity (EC 50 ) of these responses were evident in lean, obese, and diabetic subjects [”
BackgroundInsulin Action Is Associated With Endothelial Function in Hypertension and Type 2 Diabetes
Cleland, S. J., Petrie, J. R., SMALL, M. P., Elliott, H. L., & Connell, J. (2000) · Hypertension · doi:10.1161/01.hyp.35.1.507 · Cited by 126 · see citing works
Hayden, J. M., & Reaven, P. D. (2000) · Current Opinion in Lipidology · doi:10.1097/00041433-200010000-00010 · Cited by 121 · see citing works
Hulett, N. A., Scalzo, R. L., & Reusch, J. E. B. (2022) · Nutrients · doi:10.3390/nu14030647 · Cited by 125 · see citing works
“Experimental disruption of insulin signaling to eNOS, either globally or specifically in the skeletal muscle, lowers whole-body glucose disposal [11].”
BackgroundScherrer, U., & Sartori, C. S. (2000) · European Journal of Endocrinology · doi:10.1530/eje.0.1420315 · Cited by 117 · see citing works
Role of insulin resistance in the pathogenesis of NIDDM
Yki-J�rvinen, H. (1995) · Diabetologia · doi:10.1007/bf00400597 · Cited by 116 · see citing works
“Thus, defects in insulin action on blood flow have been described in both obese subjects [68], and patients with IDDM [70], NIDDM [71] and essential hypertension [72], when glucose uptake has been measured during high-dose insulin infusions lasting up to 9 h.”
BackgroundNitric oxide directly promotes vascular endothelial insulin transport
Wang, H., Wang, A. X., Aylor, K., & Barrett, E. J. (2013) · Diabetes · doi:10.2337/db13-0627 · Cited by 117 · see citing works
“Knockout of eNOS or inhibiting insulin signaling by endothelium-specific knock out of IRS-2 leading to the reduction of eNOS activity in the vascular endothelial cell produces metabolic insulin resistance (9;10).”
Insulin reduces contraction and intracellular calcium concentration in vascular smooth muscle.
Kahn, A. M., Seidel, C. L., Allen, J. C., O’Neil, R. G., Shelat, H. S., & Song, T. (1993) · Hypertension · doi:10.1161/01.hyp.22.5.735 · Cited by 116 · see citing works
Buchanan, T. A., Thawani, H., Kades, W. W., Modrall, J. G., Weaver, F. A., Laurel, C., Poppiti, R., Xiang, A. H., & Hsueh, W. A. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116642 · Cited by 114 · see citing works
Jaap, A. J., Shore, A. C., & Tooke, J. E. (1997) · Diabetologia · doi:10.1007/s001250050669 · Cited by 114 · see citing works
“Insulin resistant states have been associated with both defective insulin-mediated vasodilation [33] and endothelium-dependent vasodilation [34], suggesting the presence of ‘vascular insulin resistance’.”
Delayed Transcapillary Transport of Insulin to Muscle Interstitial Fluid in Obese Subjects
Sjöstrand, M., Gudbjörnsdottir, S., Holmäng, A., Lönn, L., Strindberg, L., & Lönnroth, P. (2002) · Diabetes · doi:10.2337/diabetes.51.9.2742 · Cited by 114 · see citing works
“Muscle perfusion correlates positively with insulinmediated glucose uptake in muscle (33,37,38).”
Anfossi, G., Mularoni, E., Burzacca, S., Ponziani, M. C., Massucco, P., Mattiello, L., Cavalot, F. L., & Trovati, M. (1998) · Diabetes Care · doi:10.2337/diacare.21.1.121 · Cited by 107 · see citing works
“N1DDM patients present an impaired vascular relaxation in response to insulin (30), to acetylcholine (a classic endothelium-dependent vasodilator, acting by increasing the endothelial production of NO) (31), and to GTN, employed as a model of endothelium-independent vasodilator (31).”
MethodInsulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA
Sydow, K., Mondon, C. E., & Cooke, J. P. (2005) · Vascular Medicine · doi:10.1177/1358836x0501000106 · Cited by 112 · see citing works
Zierath, J. R., Galuska, D., Nolte, L. A., Th�rne, A., Kristensen, J. S., & Wallberg‐Henriksson, H. (1994) · Diabetologia · doi:10.1007/bf00398054 · Cited by 106 · see citing works
“This discrepancy between in vivo and in vitro rates of glucose uptake may be explained by the observation that insulin action on the tissue level in vivo is affected in part by blood flow changes [34, 35, 37 ] as well as counterregulatory hormones [38].”
BackgroundClerk, L. H., Keske, M. A., Lindner, J. R., Clark, M. G., Rattigan, S., & Barrett, E. J. (2003) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.414 · Cited by 104 · see citing works
Montagnani, M., & Quon, M. J. (2000) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.2000.00092.x · Cited by 102 · see citing works
Jansson, Larsson, & LÖnnroth (1998) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1998.00360.x · Cited by 101 · see citing works
INSULIN AS A VASCULAR HORMONE: IMPLICATIONS FOR THE PATHOPHYSIOLOGY OF CARDIOVASCULAR DISEASE
Cleland, S. J., Petrie, J. R., Ueda, S., Elliott, H. L., & Connell, J. (1998) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.1998.t01-15-.x · Cited by 102 · see citing works
Insulin and the Vasculature—Old Actors, New Roles
Baron, A. (1996) · Journal of Investigative Medicine · doi:10.1177/108155899604400805 · Cited by 102 · see citing works
Self-citationBaron, A. (1993) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(05)80241-1 · Cited by 100 · see citing works
Self-citationDefective Endothelium-Dependent Relaxation in Fructose-Hypertensive Rats
Verma, S. (1996) · American Journal of Hypertension · doi:10.1016/0895-7061(95)00392-4 · Cited by 99 · see citing works
Rask‐Madsen, C., Ihlemann, N., Krarup, T., Christiansen, E., Køber, L., Kistorp, C. N., & Torp-Pedersen, C. T. (2001) · Diabetes · doi:10.2337/diabetes.50.11.2611 · Cited by 100 · see citing works
Gudbjörnsdóttir, S., Sjöstrand, M., Strindberg, L., Wahren, J., & Lönnroth, P. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030434 · Cited by 98 · see citing works
Nyholm, B., Mengel, A., Nielsen, S., Skjærbæk, C. B., Møller, N., Alberti, K. G. M. M., & Schmitz, O. (1996) · Diabetologia · doi:10.1007/s001250050515 · Cited by 94 · see citing works
“As ment ioned before a reduced insulin-stimulated blood flow has been suggested to be one cardinal factor behind insulin resistance in obesity and N I D D M [23-26].”
BackgroundADOLESCENTS WITH TYPE 2 DIABETES
Bronson-Castain, K., Bearse, M. A., Neuville, J., Jónasdóttir, S. G., King-Hooper, B., Barez, S., Schneck, M. E., & Adams, A. J. (2009) · Retina · doi:10.1097/iae.0b013e31819a988b · Cited by 94 · see citing works
Jagasia, D. H., Whiting, J. M., Concato, J., Pfau, S. E., & McNulty, P. H. (2001) · Circulation · doi:10.1161/01.cir.103.13.1734 · Cited by 92 · see citing works
Free fatty acids and type 2 diabetes mellitus
Wyne, K. L. (2003) · The American Journal of Medicine · doi:10.1016/j.amjmed.2003.09.004 · Cited by 90 · see citing works
Insulin resistance and vasodilation in essential hypertension. Studies with adenosine.
Natali, A., Bonadonna, R. C., Santoro, D., Galvan, A. Q., Baldi, S., Frascerra, S., Palombo, C., Ghione, S., & Ferrannini, E. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117498 · Cited by 89 · see citing works
- Authors
- Laakso, M., Edelman, S. V., Brechtel, G., & Baron, A. D.
- Affiliations
- University of California San Diego (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1992-09-01
- Volume
- 41
- Issue
- 9
- Pages
- 1076-1083
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W1984231396
- Cited by
- 470
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 10 · 2021: 5 · 2020: 4 · 2019: 10 · 2018: 4 · 2017: 7 · 2016: 7 · 2015: 14 · 2014: 7 · 2013: 9 · 2012: 7
- FWCI
- 14.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of California, Irvine
- National Institute of Diabetes and Digestive and Kidney Diseases (DK42469)
- National Center for Research Resources (M-01RR00827, M01RR000827)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 2 diabetes, skeletal muscle blood flow, insulin-stimulated glucose uptake, insulin resistance, obesity, arteriovenous glucose difference, insulin dose-response, euglycemic clamp, femoral blood flow, glucose tolerance
- MeSH terms
- Adult, Blood Glucose, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Glucose, Humans, Insulin, Leg, Muscles, Obesity, Regional Blood Flow
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
