Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects

Kingwell, Bronwyn A.; Formosa, Melissa F.; Muhlmann, M.; Bradley, Scott J.; McConell, Glenn K.

doi:10.2337/diabetes.51.8.2572

Cited by 129 publications

(146 citation statements)

References 60 publications

(86 reference statements)

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“…Nitro-L-argininemethyl-ester added to the drinking water of SpragueDawley rats prior to a 45-min exhaustive treadmill run, reduced contraction-stimulated SLC2A4 translocation and glucose transport [31]. In humans, N G -monomethyl-L-arginine administered into the femoral artery during exercise reduced glucose uptake in healthy individuals [20] and to a greater extent in patients with type 2 diabetes [21]. This occurred in the absence of any change in total leg blood flow or insulin levels [20,21].…”

Section: Discussionmentioning

confidence: 99%

“…The artery was cannulated ∼2 cm and the vein ∼4 cm below the inguinal ligament, and the catheters advanced ∼10 cm and ∼4 cm centrally, respectively. A thermistor probe (Edslab 94-030-2.5 F; Baxter Healthcare, Irvine, CA, USA) was inserted through the venous catheter and advanced ∼8 cm beyond the catheter tip [20,21]. The catheters were used for simultaneous arterial and venous blood sampling, arterial blood pressure measurement, arterial drug infusions and for venous blood flow measurement.…”

Section: Methodsmentioning

confidence: 99%

“…Right femoral venous blood flow was measured by constant-rate infusion of cold saline according to the thermodilution principle before and after each drug infusion [20,21,23]. Cold saline was drawn from a reservoir, and then immediately infused through the femoral venous catheter (5-8°C) using an Angiomat 3000 Injector (LeibelFlarsheim, Sybron Corporation, Cincinnati, OH, USA).…”

Section: Leg Blood Flowmentioning

confidence: 99%

“…Of clinical relevance is the observation that NOS inhibition during cycle exercise reduced leg glucose uptake by 48% in young, healthy humans independently of effects on leg blood flow or plasma insulin levels [20]. In patients with type 2 diabetes NOS inhibition during cycle exercise had a more pronounced effect, reducing leg glucose uptake by 75% [21]. This suggests that patients with type 2 diabetes may compensate for impaired insulin action through augmented NO-mediated glucose uptake [21].…”

Section: Introductionmentioning

confidence: 99%

“…In patients with type 2 diabetes NOS inhibition during cycle exercise had a more pronounced effect, reducing leg glucose uptake by 75% [21]. This suggests that patients with type 2 diabetes may compensate for impaired insulin action through augmented NO-mediated glucose uptake [21]. Whether exogenously delivered NO can improve glucose uptake at rest in patients with type 2 diabetes is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

et al. 2005

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Aims/hypothesis: Nitric oxide (NO) has been implicated as an important signalling molecule in the contraction-mediated glucose uptake pathway and may represent a novel strategy for blood glucose control. The current study sought to determine whether acute infusion of the NO donor, sodium nitroprusside (SNP), increases leg glucose uptake at rest in patients with type 2 diabetes. Methods: Fifteen male patients with type 2 diabetes (aged 54±4 years, mean±SD) were entered into a randomised, cross-over design study, examining the effect of a 30-min intra-femoral infusion of SNP on leg glucose uptake. Comparison was made with a 30-min infusion of verapamil, titrated to elicit similar leg blood flow responses to SNP. Leg blood flow was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of leg blood flow and the femoral arterio-venous (A-V) glucose concentration gradient. Results: The two drugs increased leg blood flow to a similar extent (p= 0.50). Both leg A-V glucose concentration gradient (SNP 0.12±0.05, verapamil −0.06±0.04 mmol/l; mean±SEM, p=0.03) and leg glucose uptake (SNP 0.17±0.09, verapamil −0.09±0.06 mmol/min; p=0.03) were higher with the SNP treatment than with verapamil. These results occurred independently of any significant difference in plasma insulin concentration between drugs (p=0.56). Conclusions/interpretation: Acute infusion of SNP resulted in greater glucose uptake relative to verapamil. NO may therefore be an important mediator of peripheral glucose disposal and a potential therapeutic target in patients with type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Leg Blood Flowmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

et al. 2005

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Exercise

Galbo¹,

Richter²

2004

International Textbook of Diabetes Mellitus

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If type 1 diabetic patients take too little insulin, exercise accelerates the rate at which hyperglycemia and ketosis develop. On the other hand, if the patients take too much insulin, hypoglycemia develops more rapidly, if they also exercise. However, education and home monitoring of blood glucose concentrations allow insulin‐treated diabetic patients to change amount and timing of insulin and food intake to cope with any exercise challenge. In type 2 diabetic patients the metabolic risks with exercise are less. In the postprandial state exercise always reduces glucose levels, and the decrease seems determined primarily by overall energy expenditure. In response to regularly repeated exercise, i.e. training, type 2 diabetic patients show an increase in insulin sensitivity in muscle and a reduction in HbA 1c levels. In contrast, type 1 diabetic patients cannot be recommended training as a means to improve glycemic control. However, in addition to mental and social benefits both groups may achieve improvements in aerobic exercise capacity, muscle strength, arterial blood pressure, and endothelium‐dependent vasodilation by training. Furthermore, cardiovascular morbidity and mortality are lower and life expectancy increased in physically active compared with sedentary diabetic patients. The risk of getting type 2 diabetes can also be reduced by an active life style. Before increasing the level of physical activity all diabetic patients should undergo a thorough medical evaluation. In case of overt or suspected clinically silent long‐term complications the examination should include a graded exercise test with ECG and blood pressure measurement. Based on the examination an appropriate program, which accounts for individual limitations and preferences and includes, for instance, both aerobic and resistance training, can be worked out for all patients.

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Exercise

Galbo

Richter

2015

International Textbook of Diabetes Mellitus

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Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects

Cited by 129 publications

References 60 publications

Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

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