Serotonin inhibition of 1‐methylxanthine metabolism parallels its vasoconstrictor activity and inhibition of oxygen uptake in perfused rat hindlimb

Rattigan, Stephen; Appleby, Geoffrey J.; Miller, Kelly A.; Steen, John; Dora, K A; Colquhoun, Eric Q.; Clark, Michael G.

doi:10.1046/j.1365-201x.1997.00215.x

Cited by 37 publications

(49 citation statements)

References 19 publications

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“…The concentration in plasma was corrected for the volume accessible to 1-MX, determined from plasma concentrations obtained after additions of standard 1-MX to whole rat blood to be 87.1%. The rate of 1-MX metabolism across the hind leg (expressed as nmol/min) reflects conversion by capillary endothelial xanthine oxidase to the sole product, 1-methyl urate [25].…”

Section: Methodsmentioning

confidence: 99%

“…Values are means±SE for n=8-10 in each group. *p<0.05 difference from Sal; # p<0.05 difference from Ins Xanthine oxidase activity Metabolism of 1-MX by xanthine oxidase of the hind limb muscle vasculature, which is measured under saturating conditions of 1-MX, has been shown to reflect changes in nutritive flow [25,28]. However, because conditions are saturating, a change in the level of xanthine oxidase activity could also influence the rate of metabolism of 1-MX.…”

Section: -Mx Metabolismmentioning

confidence: 99%

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Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment

et al. 2005

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Aims/hypothesis: Glucose toxicity and glucosamine-induced insulin resistance have been attributed to products of glucosamine metabolism. In addition, endothelial cell nitric oxide synthase is inhibited by glucosamine. Since insulin has endothelial nitric-oxide-dependent vasodilatory effects in muscle, we hypothesise that glucosamine-induced insulin resistance in muscle in vivo is associated with impaired vascular responses including capillary recruitment. Materials and methods: Glucosamine (6.48 mg kg −1 min −1 for 3 h) was infused with or without insulin (10 mU kg −1 min −1 ) into anaesthetised rats under euglycaemic conditions. Results: Glucosamine infusion alone increased blood glucosamine (1.9±0.1 mmol/l) and glucose (5.4±0.2 to 7.7± 0.3 mmol/l) (p<0.05) but not insulin. Glucosamine induced both hepatic and muscle insulin resistance as evident from measures of glucose appearance and disposal as well as hindleg glucose uptake, which was inhibited by approx. 50% (p<0.05). Insulin-mediated increases in femoral arterial blood flow and capillary recruitment were completely blocked by glucosamine. Conclusion/interpretation: Glucosamine mediates a major impairment of insulin action in muscle vasculature associated with the insulin resistance of muscle. Further studies will be required to assess whether the impaired capillary recruitment contributes to insulin resistance.

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Section: Methodsmentioning

confidence: 99%

Section: -Mx Metabolismmentioning

confidence: 99%

Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment

et al. 2005

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“…Others have shown that xanthine oxidase is predominantly located in capillary endothelial cells (29), and on this basis, we conducted experiments to see whether the metabolism of infused 1-MX, targeted for the capillary endothelial cells, changed in proportion to nutritive (capillary) flow. We found that when flow was predominantly non-nutritive, metabolism of 1-MX was markedly reduced (30), and when flow was predominantly nutritive, as with exercise, metabolism was increased (31). On this basis, 1-MX metabolism was used to assess changes in capillary recruitment due to insulin under normal conditions (21), when non-nutritive flow predominated (23), and in the presence of TNF-␣ (24).…”

Section: Discussionmentioning

confidence: 99%

Exercise Training Improves Insulin-Mediated Capillary Recruitment in Association With Glucose Uptake in Rat Hindlimb

et al. 2001

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Exercise training is considered to be beneficial in the treatment and prevention of insulin insensitivity, and much of the effect occurs in muscle. We have recently shown that capillary recruitment by insulin in vivo is associated with and may facilitate insulin action to increase muscle glucose uptake. In the present study, we examined the effect of 14 days of voluntary exercise training on euglycemic-hyperinsulinemic clamped (10 mU ⅐ min ؊1 ⅐ kg ؊1 for 2 h), anesthetized rats. Whole-body glucose infusion rate (GIR), hindleg glucose uptake, femoral blood flow (FBF), vascular resistance, and capillary recruitment, as measured by metabolism of infused 1-methylxanthine (1-MX), were assessed. In sedentary animals, insulin caused a significant (P < 0.05) increase in FBF (1.6-fold) and capillary recruitment (1.7-fold) but a significant decrease in vascular resistance. In addition, hindleg glucose uptake was increased (4.3-fold). Exercise training increased insulin-mediated GIR (24%), hindleg glucose uptake (93%), and capillary recruitment (62%) relative to sedentary animals. Neither capillary density nor total xanthineoxidase activity in skeletal muscle were increased as a result of the training regimen used. We concluded that exercise training improves insulin-mediated increases in capillary recruitment in combination with augmented muscle glucose uptake. Increased insulin-mediated glucose uptake may in part result from the improved hemodynamic control attributable to exercise training.

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“…The concentration in plasma was corrected for the volume accessible to 1-MX, determined from plasma concentrations obtained after additions of standard 1-MX to whole rat blood to be 87.1%. The rate of 1-MX metabolism across the hindlimb (expressed as nmol·min −1 ) reflects conversion by capillary endothelial xanthine oxidase to the sole product, 1-methyl urate [19].…”

Section: Methodsmentioning

confidence: 99%

Local methacholine but not bradykinin potentiates insulin-mediated glucose uptake in muscle in vivo by augmenting capillary recruitment

et al. 2004

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Aims/hypothesis. Insulin has nitric-oxide-dependent vasodilatory effects in muscle, including capillary recruitment, that enhance access for itself and glucose. However, nitric-oxide-dependent vasodilators other than methacholine do not enhance insulin action. Our hypothesis is that methacholine, unlike bradykinin, enhances insulin-mediated glucose uptake in muscle by augmenting capillary recruitment. Methods. Local infusion of either methacholine or bradykinin into one leg of the anaesthetised rat was made during physiological insulin (3 mU·kg −1 ·min −1 ) infusion under euglycaemic conditions and without affecting systemic blood pressure. Whole-body glucose infusion was determined, as was femoral blood flow, 2-deoxyglucose uptake into calf muscles and the metabolism of infused 1-methylxanthine, a measure of capillary recruitment for each leg. Results. Methacholine alone (0.3 µmol·l -1 ) increased femoral arterial blood flow, increased capillary recruitment but had no effect on 2-deoxyglucose uptake of the test leg relative to the contra-lateral control leg. Insulin alone (systemically) required a glucose infusion rate of 8.7 mg·kg −1 ·min −1 to maintain euglycaemia, increased 2-deoxyglucose uptake and capillary recruitment, but was without effect on femoral blood flow in either leg. Local methacholine with systemic insulin infusion increased femoral blood flow, 2-deoxyglucose uptake and capillary recruitment in the test leg only. Bradykinin (0.07 µmol·l -1 ), alone or with insulin, administered in a manner that increased femoral blood flow similarly to methacholine, did not affect 2-deoxyglucose uptake or capillary recruitment. Conclusions/interpretation. Methacholine but not bradykinin enhances insulin-mediated muscle glucose uptake in vivo. We conclude that methacholine acts at specific sites in the vasculature of muscle to stimulate capillary recruitment and thereby enhance insulin access.Keywords Global vasodilatation in muscle · Insulin and glucose delivery to muscle · Muscle blood flow · Specific regional vasodilatation in muscle.

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Serotonin inhibition of 1‐methylxanthine metabolism parallels its vasoconstrictor activity and inhibition of oxygen uptake in perfused rat hindlimb

Cited by 37 publications

References 19 publications

Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment

Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment

Exercise Training Improves Insulin-Mediated Capillary Recruitment in Association With Glucose Uptake in Rat Hindlimb

Local methacholine but not bradykinin potentiates insulin-mediated glucose uptake in muscle in vivo by augmenting capillary recruitment

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