Cited by 470Diabetes, Cardiovascular Risks, and LipoproteinsMetabolism, Diabetes, and CancerDiabetes Management and Research

The DOI matches its Crossref record.

Impaired Insulin-Mediated Skeletal Muscle Blood Flow in Patients With NIDDM

Laakso, Markku, Edelman, Steven V, Brechtel, Ginger, Baron, Alain D·1992·Diabetes

DOI 10.2337/diab.41.9.1076

Open this paper in CoChat — free account

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

Crossref · 10.2337/diab.41.9.1076

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Sorted by citations

Items 101–200 of 457

Hyperinsulinemia Rapidly Increases Human Muscle Microvascular Perfusion but Fails to Increase Muscle Insulin Clearance
Eggleston, E., Jahn, L. A., & Barrett, E. J. (2007) · Diabetes · doi:10.2337/db07-0670 · Cited by 88
Perivascular fatty tissue at the brachial artery is linked to insulin resistance but not to local endothelial dysfunction
Rittig, K., Staib, K., Machann, J., Bøttcher, M., Peter, A., Schick, F., Claussen, C. D., Stefan, N., Fritsche, A., Häring, H., et al. (2008) · Diabetologia · doi:10.1007/s00125-008-1128-3 · Cited by 87
“In previous studies, muscle perfusion has been shown to modulate insulinmediated glucose uptake [20–22], which is reduced in the insulin-resistant state [23, 24].”
Background
Non-insulin-dependent Diabetes Mellitus - A Collision between Thrifty Genes and an Affluent Society
Groop, L., & Tuomi, T. (1997) · Annals of Medicine · doi:10.3109/07853899708998742 · Cited by 88
Antihypertensive therapy with enalapril improves glucose storage and insulin sensitivity in hypertensive patients with non—insulin-dependent diabetes mellitus
Vuorinen-Markkola, H., & Yki‐Järvinen, H. (1995) · Metabolism · doi:10.1016/0026-0495(95)90293-7 · Cited by 86
FFA-Induced Endothelial Dysfunction Can Be Corrected by Vitamin C
Pleiner, J., Schaller, G., Mittermayer, F., Bayerle‐Eder, M., Roden, M., & Wolzt, M. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.6.8596 · Cited by 87
Clustering of Endothelial Markers of Vascular Damage in Human Salt-Sensitive Hypertension
Ferri, C., Bellini, C., Desideri, G., Giuliani, E., Siati, L. D., Cicogna, S., & Santucci, A. (1998) · Hypertension · doi:10.1161/01.hyp.32.5.862 · Cited by 81
Targeting postprandial hyperglycemia
Rendell, M., & Jovanovič, L. (2006) · Metabolism · doi:10.1016/j.metabol.2006.05.012 · Cited by 80
Influence of insulin and of insulin resistance on platelet and vascular smooth muscle cell function
Trovati, M., & Anfossi, G. (2002) · Journal of Diabetes and its Complications · doi:10.1016/s1056-8727(01)00196-9 · Cited by 81
Decreased Muscle Capillary Permeability Surface Area in Type 2 Diabetic Subjects
Guðbjörnsdóttir, S., Sjöstrand, M., Strindberg, L., & Lönnroth, P. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0947 · Cited by 81
Insulin Improves Myocardial Blood Flow in Patients With Type 2 Diabetes and Coronary Artery Disease
Läutamaki, R., Airaksinen, J. K. E., Seppänen, M., Toikka, J., Härkönen, R., Luotolahti, M., Borra, R., Sundell, J., Knuuti, J. M., & Nuutila, P. (2006) · Diabetes · doi:10.2337/diabetes.55.02.06.db05-1023 · Cited by 79
The metabolic syndrome: Insulin resistance
Mikhail, N. E. (2009) · Current Hypertension Reports · doi:10.1007/s11906-009-0027-4 · Cited by 81
“However, some studies have shown that the vasodilator action of insulin may be blunted in insulinresistant states such as obesity and type 2 diabetes [15, 16 ].”
Background
Relationship between autonomic dysfunction, insulin resistance and hypertension, in diabetes
Frontoni, S., Bracaglia, D., & Gigli, F. (2005) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2005.06.010 · Cited by 81
“It is well known that a high degree of correlation exists between the extent of vasodilation and insulin-stimulated glucose uptake [47], and on the other hand, several studies demonstrated a blunted insulin-mediated vasodilation [48] in insulin-resistant states.”
Background
Glucose transport in brain and retina: implications in the management and complications of diabetes
Kumagai, A. K. (1999) · Diabetes/Metabolism Research and Reviews · doi:10.1002/(sici)1520-7560(199907/08)15:4 · Cited by 159
Metabolic and vascular insulin resistance: partners in the pathogenesis of cardiovascular disease in diabetes
Horton, W. B., Love, K. M., Gregory, J. M., Liu, Z., & Barrett, E. J. (2025) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00826.2024 · Cited by 95
Activation of the Sodium-Potassium Pump Contributes to Insulin-Induced Vasodilation in Humans
Tack, C. J., Lutterman, J. A., Vervoort, G., Thien, T. A., & Smits, P. (1996) · Hypertension · doi:10.1161/01.hyp.28.3.426 · Cited by 78
Actions of Peroxisome Proliferator–Activated Receptors–γ Agonists Explaining a Possible Blood Pressure–Lowering Effect
Sarafidis, P. A., & Lasaridis, A. N. (2006) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2005.12.017 · Cited by 78
Intact insulin stimulation of skeletal muscle blood flow, its heterogeneity and redistribution, but not of glucose uptake in non-insulin-dependent diabetes mellitus.
Utriainen, T., Nuutila, P., Takala, T., Vicini, P., Ruotsalainen, U., Rönnemaa, T., Tolvanen, T., Raitakari, M., Haaparanta‐Solin, M., Kirvelä, O., et al. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119591 · Cited by 75
“In previous human studies, mean limb blood flows have been measured using techniques such as plethysmography (4, 14–17), thermo- (6, 18) and dye- (2, 19) dilution, and more recently, [ 15 O]H 2 O and positron emission tomography (PET) (20–22).”
BackgroundMethodInfluential
Association of (−)786T–C mutation of endothelial nitric oxide synthase gene with insulin resistance
K., O., Y., Y., S., G., R., H.-O., K., N., M., M., Y., K., & M., H. (2002) · Diabetologia · doi:10.1007/s00125-002-0922-6 · Cited by 71
Vascular function, insulin action, and exercise: an intricate interplay
Zheng, C., & Liu, Z. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.02.002 · Cited by 73
“This group of investigators also confirmed a coupling of insulin’s vascular effects and metabolic effects by demonstrating that changes in insulin-mediated leg blood flow were paralleled by changes in insulin-mediated glucose disposal in leg in healthy humans as well as in subjects with obesity [30], type 1 diabetes […”
Background
Arteriolar nitric oxide concentration is decreased during hyperglycemia-induced βII PKC activation
Bohlen, H. G., & Nase, G. P. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.280.2.h621 · Cited by 70
Dose-Dependent Vasodilating Effects of Insulin on Adenosine-Stimulated Myocardial Blood Flow
Sundell, J., Nuutila, P., Laine, H. K., Luotolahti, M., Kalliokoski, K. K., Raitakari, O. T., & Knuuti, J. M. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1125 · Cited by 70
“Insulin induces a dose-dependent vasodilation in the peripheral arteries (9–11) that is blunted in insulin-resistant states (10,12,13).”
Background
Insulin Sensitivity, Vascular Reactivity, and Clamp-Induced Vasodilatation in Essential Hypertension
Natali, A., Taddei, S., Galvan, A. Q., Camastra, S., Baldi, S., Frascerra, S., Virdis, A., Sudano, I., Salvetti, A., & Ferrannini, E. (1997) · Circulation · doi:10.1161/01.cir.96.3.849 · Cited by 71
The Regulation of Body and Skeletal Muscle Protein Metabolism by Hormones and Amino Acids
Liu, Z., Long, W., Fryburg, D. A., & Barrett, E. J. (2006) · Journal of Nutrition · doi:10.1093/jn/136.1.212s · Cited by 69
1 Cellular insulin action and insulin resistance
Garvey, W. T., & Birnbaum, M. J. (1993) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(05)80237-x · Cited by 67
Association of Resistin Gene 3′-Untranslated Region +62G→A Polymorphism with Type 2 Diabetes and Hypertension in a Chinese Population
Tan, M., Chang, S.-Y., Chang, D., Tsai, J. C. ‐., & Lee, Y. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021453 · Cited by 70
In VivoInsulin-Dependent Glucose Uptake of Specific Tissues Is Decreased during Aging of Mature Wistar Rats1
Escrivá, F., Agote, M., Rubio, E., Molero, J. C., Pascual-Leone, A. M., Andrés, A., Satrústegui, J., & Carrascosa, J. M. (1997) · Endocrinology · doi:10.1210/endo.138.1.4862 · Cited by 69
Insulin Resistance and the Effect of Insulin on Blood Pressure in Essential Hypertension
Heise, T., Magnusson, K., Heinemann, L., & Sawicki, P. T. (1998) · Hypertension · doi:10.1161/01.hyp.32.2.243 · Cited by 69
Endurance, interval sprint, and resistance exercise training: impact on microvascular dysfunction in type 2 diabetes
Olver, T. D., & Laughlin, M. H. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00440.2015 · Cited by 67
“Insulin-stimulated increases in skeletal muscle blood flow and lower limb vascular conductance are blunted in patients with T2D (65, 75).”
Interactions between insulin and norepinephrine on blood pressure and insulin sensitivity. Studies in lean and obese men.
Baron, A., Brechtel, G., Johnson, A., Fineberg, N. S., Henry, D. P., & Steinberg, H. O. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117254 · Cited by 67
Self-citation
Contrasting Autonomic and Hemodynamic Effects of Insulin in Healthy Elderly Versus Young Subjects
Hausberg, M., Hoffman, R. P., Somers, V. K., Sinkey, C. A., Mark, A. L., & Anderson, E. A. (1997) · Hypertension · doi:10.1161/01.hyp.29.3.700 · Cited by 68
Insulin, nitric oxide and the sympathetic nervous system
Sartori, C. S., & Scherrer, U. (1999) · Journal of Hypertension · doi:10.1097/00004872-199917110-00003 · Cited by 67
Long-term fructose feeding impairs vascular relaxation in rat mesenteric arteries
Takagawa, Y., Berger, M. E., Hori, M., Tuck, M. L., & Golub, M. S. (2001) · American Journal of Hypertension · doi:10.1016/s0895-7061(01)01298-5 · Cited by 66
METABOLIC COMPLICATIONS OF OBESITY
Sheehan, M. T., & Jensen, M. D. (2000) · Medical Clinics of North America · doi:10.1016/s0025-7125(05)70226-1 · Cited by 68
Physiology in Medicine: neuromuscular consequences of diabetic neuropathy
Allen, M. D., Doherty, T. J., Rice, C. L., & Kimpinski, K. (2016) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00733.2015 · Cited by 66
“Furthermore, DM is closely linked with dysfunction in microvasculature as well as slowed oxygen kinetics during exercise (16, 40), both of which could reduce skeletal muscle oxidative metabolism and adversely affect endurance.”
Background
Insulin and myocardial blood flow
Sundell, J. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00718-6 · Cited by 66
Muscle microvasculature's structural and functional specializations facilitate muscle metabolism
Kusters, Y. H. A. M., & Barrett, E. J. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00443.2015 · Cited by 66
The effects of thiazolidinediones on blood pressure levels – A systematic review
Sarafidis, P. A., & Nilsson, P. M. (2006) · Blood Pressure · doi:10.1080/08037050600853720 · Cited by 64
Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1
Reynolds, L. J., Credeur, D. P., Manrique, C. M., Padilla, J., Fadel, P. J., & Thyfault, J. P. (2016) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00286.2016 · Cited by 63
AKT phosphorylation is essential for insulin-induced relaxation of rat vascular smooth muscle cells
Lee, J. H., & Ragolia, L. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00125.2006 · Cited by 63
“DEFECTS IN THE RELAXATION mechanisms of smooth muscle within the blood vessels of patients with hypertension, noninsulin-dependent diabetes, and obesity have been reported in many studies (2, 40, 51, 52, 66).”
Role of Nitric Oxide, Adenosine, and ATP-Sensitive Potassium Channels in Insulin-Induced Vasodilation
McKay, M. K., & Hester, R. L. (1996) · Hypertension · doi:10.1161/01.hyp.28.2.202 · Cited by 60
INTERACTION OF PHYSIOLOGICAL MECHANISMS IN CONTROL OF MUSCLE GLUCOSE UPTAKE
Wasserman, D. H., & Ayala, J. E. (2005) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2005.04191.x · Cited by 62
Do low levels of circulating adiponectin represent a biomarker or just another risk factor for the metabolic syndrome?
Brooks, N. L., Moore, K. S., Clark, R. D., Perfetti, M. T., Trent, C. M., & Combs, T. P. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2006.00596.x · Cited by 59
Mechanisms of insulin resistance in experimental hyperinsulinemic dogs.
Miles, P. D. G., Li, S., Hart, M. A., Romeo, O. M., Cheng, J., Cohen, A., Raafat, K. M., Moossa, A. R., & Olefsky, J. M. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1256 · Cited by 59
Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries
Piatti, P., Fragasso, G., Monti, L. D., Caumo, A., Phan, C. V., Valsecchi, G., Costa, S., Fochesato, E., Pozza, G., Pontiroli, A. E., et al. (1999) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(99)00379-4 · Cited by 59
Diet-induced endothelial dysfunction in the rat is independent of the degree of increase in total body weight
Naderali, E. K., Pickavance, L. C., Wilding, J. P. H., & Williams, G. (2001) · Clinical Science · doi:10.1042/cs1000635 · Cited by 59
The edematogenic properties of insulin
Kalambokis, G. N., Tsatsoulis, A. A., & Tsianos, E. V. (2004) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2004.06.025 · Cited by 74
Time course of insulin resistance associated with feeding dogs a high-fat diet
Rocchini, A. P., Marker, P. H., & Cervenka, T. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.272.1.e147 · Cited by 59
Daily physical activity enhances reactivity to insulin in skeletal muscle arterioles of hyperphagic Otsuka Long-Evans Tokushima Fatty rats
Mikus, C. R., Rector, R. S., Arce‐Esquivel, A. A., Libla, J. L., Booth, F. W., Ibdah, J. A., Laughlin, M. H., & Thyfault, J. P. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00064.2010 · Cited by 57
Oxidative stress — mediated alterations in glucose dynamics in a genetic animal model of type II diabetes
Bitar, M. S., Al‐Saleh, E., & Al‐Mulla, F. (2005) · Life Sciences · doi:10.1016/j.lfs.2005.01.033 · Cited by 57
Regional myocardial blood flow and glucose utilization during fasting and physiological hyperinsulinemia in humans
Iozzo, P., Chareonthaitawee, P., Terlizzi, M. D., Betteridge, D. J., Ferrannini, E., & Camici, P. G. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00386.2001 · Cited by 57
Exercise training improves cardiovascular autonomic modulation in response to glucose ingestion in obese adults with and without type 2 diabetes mellitus
Goulopoulou, S., Baynard, T., Franklin, R. M., Fernhall, B., Carhart, R. L., Weinstock, R. S., & Kanaley, J. A. (2009) · Metabolism · doi:10.1016/j.metabol.2009.10.011 · Cited by 56
“It has been shown that insulin-induced vasodilation is impaired in obesity and T2D [1,38,39] because of endothelial dysfunction [40].”
Background
Insulin resistance and endothelial dysfunction in type 2 diabetes patients with or without microalbuminuria
Yu, Y., Suo, L., Yu, H., Wang, C., & Tang, H. (2004) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2004.01.006 · Cited by 54
“[11,12] demonstrated that insulin resistance states, including obesity and type 2 diabetes mellitus, exhibited blunted insulin-mediated vasodilation and impaired endothelium-dependent vasodilation.”
Background
Insulin increases cyclic nucleotide content in human vascular smooth muscle cells: a mechanism potentially involved in insulin-induced modulation of vascular tone
Trovati, M., Massucco, P., Mattiello, L., Cavalot, F. L., Mularoni, E., Hahn, A., & Anfossi, G. (1995) · Diabetologia · doi:10.1007/bf00400582 · Cited by 57
Dissociation between insulin sensitivity of glucose uptake and endothelial function in normal subjects
Utriainen, T., Mäkimattila, S., Virkamäki, A., Bergholm, R., & Yki‐Järvinen, H. (1996) · Diabetologia · doi:10.1007/s001250050601 · Cited by 55
Documento de consenso: obesidad y riesgo cardiovascular
Bartrina, J. A., Foz, M., Moreno, B., Bartrina, J. A., Gil, B., Jover, E., Millán(coordinador), J., Mantilla, T., Monereo, S., & Moreno, B. (2003) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/s0214-9168(03)78933-5 · Cited by 54
Insulin and hypertension: a causal relationship?
Bhanot, S., & McNeill, J. H. (1996) · Cardiovascular Research · doi:10.1016/s0008-6363(95)00218-9 · Cited by 54
“In NIDDM patients, the EC, was about 17-fold higher, indicating a marked resistance to the vasodilator effects of insulin [118].”
Background
Estimations of muscle interstitial insulin, glucose, and lactate in type 2 diabetic subjects
Sjöstrand, M., Holmäng, A. B., Strindberg, L., & Lönnroth, P. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.279.5.e1097 · Cited by 53
Heightened norepinephrine-mediated vasoconstriction in type 2 diabetes
Hogikyan, R. V., Gałecki, A. T., Halter, J. B., & Supiano, M. A. (1999) · Metabolism · doi:10.1016/s0026-0495(99)90242-1 · Cited by 54
l-Leucine and NO-mediated cardiovascular function
Yang, Y., Wu, Z., Meininger, C. J., & Wu, G. (2014) · Amino Acids · doi:10.1007/s00726-014-1904-y · Cited by 53
“…indicate that sensitivity of blood vessels to the vasodilatory effect of insulin is positively correlated with insulin signaling with respect to glucose uptake under normal, obese and diabetic conditions (Baron et al. 1993; Baron and Brechtel 1993; Ding et al. 2000; Laakso et al. 1990, 1992).”
Background
Obesity and Endothelial Dysfunction
Shankar, S. S., & Steinberg, H. O. (2005) · Seminars in Vascular Medicine · doi:10.1055/s-2005-871742 · Cited by 51
Insulin‐induced membrane permeability to glucose in human muscles at rest and following exercise
McConell, G. K., Sjøberg, K. A., Ceutz, F. R., Gliemann, L., Nyberg, M., Hellsten, Y., Frøsig, C., Kiens, B., Wojtaszewski, J. F. P., & Richter, E. A. (2019) · The Journal of Physiology · doi:10.1113/jp278600 · Cited by 50
“However, given people with T2D have endothelial dysfunction which manifests as impaired blood flow response to both insulin (Laakso et al. 1992) and exercise (Kingwell et al. 2002) and also have decreased GLUT4 translocation in response to insulin (Ryder et al. 2000), it is difficult to predict the…”
Background
Changes in blood pressure and plasma catecholamine levels during prolonged hyperinsulinemia
Kern, W., Peters, A., Jan Born, A., Fehm, H. L., & Schultes, B. (2005) · Metabolism · doi:10.1016/j.metabol.2004.10.005 · Cited by 50
“In this context, it is worth mentioning that there is evidence that in the condition of chronic hyperinsulinemia the hormone loses its vasodilatory action [32,51,52], whereas its stimulatory influence on the sympathetic nervous systems remains preserved [17-19,25].”
Background
Vasodilator Response to Systemic But Not to Local Hyperinsulinemia in the Human Forearm
Cardillo, C., Kilcoyne, C. M., Nambi, S., Cannon, R. O., Quon, M. J., & Panza, J. A. (1998) · Hypertension · doi:10.1161/01.hyp.32.4.740 · Cited by 51
Effects of short-term inactivity on glucose tolerance, energy expenditure, and blood flow in trained subjects
Arciero, P. J., Smith, D. L., & Calles-Escandon, J. (1998) · Journal of Applied Physiology · doi:10.1152/jappl.1998.84.4.1365 · Cited by 50
“(17) suggest that the blunted hemodynamic response to physiological insulin levels in subjects with non-insulinmediated diabetes mellitus vs.”
Background
Increased mitochondrial content rescues in vivo muscle oxidative capacity in long‐term high‐fat‐diet‐fed rats
van den Broek, N. M. A., Čiapaitė, J., Feyter, H. M. M. L. D., Houten, S. M., Wanders, R. J. A., Jeneson, J. A. L., Nicolay, K., & Prompers, J. J. (2009) · The FASEB Journal · doi:10.1096/fj.09-143842 · Cited by 51
“Insulin regulates muscle blood flow through stimulation of nitric oxide-dependent vasodilation (50).”
Background
Combined effects of endothelial nitric oxide synthase gene polymorphism (G894T) and insulin resistance status on blood pressure and familial risk of hypertension in young adults: the Bogalusa Heart Study
Chen, W. (2001) · American Journal of Hypertension · doi:10.1016/s0895-7061(01)02192-6 · Cited by 49
“There is increasing evidence that nitric oxide synthesis and the vasodilating properties of insulin are impaired in insulin-resistant states such as obesity, type 2 diabetes, and hypertension.(16,17,19) In the current study, insulin resistance status, measured by HOMA IR, and the eNOS G894T polymorphism showed signifi…”
Background
Inhibitory Effects of Insulin on Cytosolic Ca2+Level and Contraction in the Rat Aorta
Han, S.-Z., Ouchi, Y., Karaki, H., & Orimo, H. (1995) · Circulation Research · doi:10.1161/01.res.77.4.673 · Cited by 50
Hypoglycemic pharmacological treatment of type 2 diabetes: Targeting the endothelium
Nathanson, D., & Nyström, T. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.11.016 · Cited by 48
Rosiglitazone effects on blood pressure and metabolic parameters in nondipper diabetic patients
Negro, R., Mangieri, T., Dazzi, D., Pezzarossa, A., & Hassan, H. (2005) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2005.02.012 · Cited by 49
“Insulin induces antinatriuresis, activates the sympathetic nervous system, alters the ion transport systems and induces alterations in vascular smooth muscle tone which in turn, reduces peripheral blood flow worsening insulin sensitivity [8–12].”
Background
Evidence for physiological coupling of insulin-mediated glucose metabolism and limb blood flow
Mather, K. J., Laakso, M., Edelman, S. V., Brechtel, G., & Baron, A. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.279.6.e1264 · Cited by 49
Self-citation
Type 2 Diabetes Mellitus
Polonsky, K. S., & Burant, C. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00031-9 · Cited by 53
Effect of plasma insulin level on myocardial blood flow and its mechanism of action
McNulty, P. H., Pfau, S. E., & Deckelbaum, L. I. (2000) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)00650-5 · Cited by 48
Nitric Oxide and the Cardiovascular System
Bohlen, H. G. (2015) · Comprehensive physiology · doi:10.1002/cphy.c140052 · Cited by 54
Role of postprandial hyperglycemia in cardiovascular disease
Fava, S. (2008) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.6.6.859 · Cited by 47
Insulin and renal sodium retention in hypertension-prone men.
Endre, T., Mattiasson, I., Berglund, G., & Hulthén, U. L. (1994) · Hypertension · doi:10.1161/01.hyp.23.3.313 · Cited by 47
Seven days of aerobic exercise training improves conduit artery blood flow following glucose ingestion in patients with type 2 diabetes
Mikus, C. R., Fairfax, S. T., Libla, J. L., Boyle, L. J., Vianna, L. C., Oberlin, D. J., Uptergrove, G. M., Deo, S. H., Kim, A., Kanaley, J. A., et al. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00489.2011 · Cited by 48
“However, an imbalance in the production of nitric oxide and endothelin-1 appears to blunt insulin-mediated increases in blood flow in obese and insulinresistant individuals (3, 7, 26).”
Background
Insulin resistance and maximal oxygen uptake
Seibæk, M., Vestergaard, H., Burchardt, H., Sloth, C., Torp-Pedersen, C. T., Nielsen, S. L., Hildebrandt, P. R., & Pedersen, O. B. (2003) · Clinical Cardiology · doi:10.1002/clc.4960261107 · Cited by 46
Lower-Limb Vascularization in Diabetic Patients
Cosson, E., Paycha, F., Tellier, P., Sachs, R. N., Ramadan, A., Pariès, J., Attali, J. R., & Valensi, P. E. (2001) · Diabetes Care · doi:10.2337/diacare.24.5.870 · Cited by 46
“Therefore, femoral endothelial dysfunction has also been demonstrated in type 2 diabetic patients (25).”
Background
Hyperglycaemia modifies the reaction of microvessels to insulin in rat skeletal muscle
Renaudin, C., Michoud, E., Rapin, J. R., Lagarde, M., & Wiernsperger, N. F. (1998) · Diabetologia · doi:10.1007/s001250050862 · Cited by 46
Serotonin-mediated acute insulin resistance in the perfused rat hindlimb but not in incubated muscle: A role for the vascular system
Rattigan, S., Dora, K. A., Colquhoun, E. Q., & Clark, M. G. (1993) · Life Sciences · doi:10.1016/0024-3205(93)90563-i · Cited by 46
Impaired Insulin-Induced Attenuation of Noradrenaline-Mediated Vasoconstriction in Insulin-Resistant Obese Zucker Rats
Walker, A. B., Dores, J. M., Buckingham, R. E., Savage, M. W., & Williams, G. (1997) · Clinical Science · doi:10.1042/cs0930235 · Cited by 45
Coronary artery disease, nitric oxide and oxidative stress: The "Yin-Yang" effect - a Chinese concept for a worldwide pandemic
Cook, S. (2006) · Swiss Medical Weekly · doi:10.4414/smw.2006.11068 · Cited by 45
Alterations in Nitric Oxide/Cyclic-GMP Pathway in Nondiabetic Siblings of Patients with Type 2 Diabetes1
Piatti, P., Monti, L. D., Zavaroni, I., Valsecchi, G., Phan, C. V., Costa, S., Conti, M., Sandoli, E. P., Solerte, B., Pozza, G., et al. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.7.6667 · Cited by 43
Insulin resistance, a new target for nitric oxide‐delivery drugs
Cook, S., & Scherrer, U. (2002) · Fundamental and Clinical Pharmacology · doi:10.1046/j.1472-8206.2002.00130.x · Cited by 44
Decreased muscle endurance associated with diabetic neuropathy may be attributed partially to neuromuscular transmission failure
Allen, M. D., Kimpinski, K., Doherty, T. J., & Rice, C. L. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00441.2014 · Cited by 49
“It has been reported that DM and DPN are associated with dysfunction in the macro- and microvasculature (10, 18, 22, 34, 60), as well as slowed oxygen kinetics during exercise (45, 46).”
Background
Direct Vasodepressor Effects of Pioglitazone in Spontaneously Hypertensive Rats
Verma, S., Bhanot, S., Arikawa, E., Yao, L., & McNeill, J. H. (1998) · Pharmacology · doi:10.1159/000028177 · Cited by 43
Insulin action in muscle and adipose tissue in type 2 diabetes: The significance of blood flow
Lambadiari, V., Τriantafyllou, Κ., & Dimitriadis, G. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i4.626 · Cited by 42
Erectile dysfunction: does insulin resistance play a part?
Trussell, J. C., & Legro, R. S. (2007) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.01.116 · Cited by 44
Insulin and the vasculature
Mikhail, N. E., & Tuck, M. L. (2000) · Current Hypertension Reports · doi:10.1007/s11906-000-0074-3 · Cited by 42
“However, in insulin-resistant states, such as obesity [19], and type 2 diabetes [4, 7 ], there is ample evidence that insulin-mediated vasodilatation may be blunted (Fig. 2), possibly because of defective NO synthesis resulting from endothelial dysfunction.”
BackgroundInfluential
Microvascular insulin resistance in skeletal muscle and brain occurs early in the development of juvenile obesity in pigs
Olver, T. D., Grunewald, Z. I., Jurrissen, T. J., MacPherson, R. E. K., LeBlanc, P. J., Schnurbusch, T., Czajkowski, A. M., Laughlin, M. H., Rector, R. S., Bender, S. B., et al. (2017) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00213.2017 · Cited by 45
Insulin Acutely Inhibits Cultured Vascular Smooth Muscle Cell Contraction by a Nitric Oxide Synthase–Dependent Pathway
Kahn, A. M., Husid, A., Allen, J. C., Seidel, C. L., & Song, T. (1997) · Hypertension · doi:10.1161/01.hyp.30.4.928 · Cited by 41
Insulin sensitivity and coronary vasoreactivity: insulin sensitivity relates to adenosine‐stimulated coronary flow response in human subjects
Dagres, N., Saller, B., Haude, M., Hüsing, J., von Birgelen, C., Schmermund, A., Sack, S., Baumgart, D., Mann, K., & Erbel, R. M. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02156.x · Cited by 41
“Indeed, studies in individuals with insulin-resistant states such as obesity or type 2 diabetes indicate blunted insulin-mediated vasodilation (Laakso et al., 1992; Steinberg et al., 1996; Williams et al., 1996).”
Background
Insulin Modulation of Vascular Reactivity Is Already Impaired in Prehypertensive Spontaneously Hypertensive Rats
Lembo, G., Iaccarino, G., Vecchione, C., Rendina, V., & Trimarco, B. (1995) · Hypertension · doi:10.1161/01.hyp.26.2.290 · Cited by 41
Pentoxifylline acutely reduces protein catabolism in chronically uremic patients
Biolo, G., Ciocchi, B., Bosutti, A., Situlin, R., Toigo, G., & Guarnieri, G. (2002) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2002.36864 · Cited by 39
CARDIOVASCULAR ACTIONS OF INSULIN: ARE THEY IMPORTANT IN LONG‐TERM BLOOD PRESSURE REGULATION?
Hall, J. E., Brands, M. W., Zappe, D., & Alonso‐Galicia, M. (1995) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.1995.tb01922.x · Cited by 38
Obesity Affects Myocardial Vasoreactivity and Coronary Flow Response to Insulin
Sundell, J., Laine, H. K., Luotolahti, M., Kalliokoski, K. K., Raitakari, O. T., Nuutila, P., & Knuuti, J. M. (2002) · Obesity Research · doi:10.1038/oby.2002.84 · Cited by 40
Insulin Resistance and Insulin Sensitizers
Stümvoll, M., & Häring, H. U. (2001) · Hormone Research in Paediatrics · doi:10.1159/000063466 · Cited by 42
Insulin, Muscle Glucose Uptake, and Hexokinase: Revisiting the Road Not Taken
Wasserman, D. H. (2021) · Physiology · doi:10.1152/physiol.00034.2021 · Cited by 44
Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA
Sydow, K., Mondon, C. E., & Cooke, J. P. (2005) · Vascular Medicine · doi:10.1191/1358863x05vm604oa · Cited by 39
Obesity lowers hyperglycemic threshold for impaired in vivo endothelial nitric oxide function
Bohlen, H. G., & Nase, G. P. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00019.2002 · Cited by 37

Authors: Laakso, M., Edelman, S. V., Brechtel, G., & Baron, A. D.
Affiliations: University of California San Diego (US)
ORCID: Laakso, Markku
Edelman, Steven V
Venue: Diabetes
Publisher: American Diabetes Association
Published: 1992-09-01
Volume: 41
Issue: 9
Pages: 1076-1083
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diab.41.9.1076
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

Impaired Insulin-Mediated Skeletal Muscle Blood Flow in Patients With NIDDM

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cited by

Related

Metadata

Record

About these checks