Skip to main content
Top
Published in: European Journal of Applied Physiology 2/2014

01-02-2014 | Original Article

Acute hyperglycaemia does not alter nitric oxide-mediated microvascular function in the skin of adolescents with type 1 diabetes

Authors: Louise H. Naylor, Norhaida M. Yusof, Nirubasini Paramalingam, Timothy W. Jones, Elizabeth A. Davis, Daniel J. Green

Published in: European Journal of Applied Physiology | Issue 2/2014

Login to get access

Abstract

Purpose

We assessed the impact of an acute bout of hyperglycaemia on nitric oxide (NO)-mediated microvascular function in the skin of adolescents with type 1 diabetes (T1DM).

Methods

Twelve subjects (12–18 years) with T1DM were randomised into a control (n = 6) or hyperglycaemia (n = 6) group. Hyperinsulinaemic clamps were used to manipulate blood glucose level (BGL). Following a baseline period, where all subjects were euglycaemic (20 min), the experimental phase began. During the experimental phase, BGL was elevated to 16.7 ± 0.9 mmol L−1 in the hyperglyceamic group, while it was maintained at euglycaemia (5.5 ± 0.1 mmol L−1) in the control group. Simultaneously, cutaneous microvascular function (% max cutaneous vascular conductance, CVC%) was assessed using laser Doppler fluxometry following stimulation of skin blood flow using localised heating (42 °C). To determine the NO contribution to skin blood flow, two microdialysis sites were assessed, one perfused with Ringers and the other with the NO blocker, NG-monomethyl-l-arginine (l-NMMA).

Results

In the hyperglycaemic group, acute increase in BGL was not associated with changes in skin blood flow (CVC% 82.4 ± 8.7 % at 5.5 ± 0.1 mmol L−1 vs 79.5 ± 9.1 % at 16.7 ± 0.9 mmol L−1, unpaired t tests, P = 0.588) or the contribution of NO to vasodilation.

Conclusions

These results suggest that, in our group of adolescents with type 1 diabetes, acute hyperglycaemia did not affect skin microvascular NO-mediated function.
Literature
go back to reference Akbari C, Saouaf R, Barnhill D, Newman P, LoGerfo F, Veves A (1998) Endothelium-dependent vasodilatation is impaired in both microcirculation and macrocirculation during acute hyperglycemia. J Vasc Surg 28:687–694PubMedCrossRef Akbari C, Saouaf R, Barnhill D, Newman P, LoGerfo F, Veves A (1998) Endothelium-dependent vasodilatation is impaired in both microcirculation and macrocirculation during acute hyperglycemia. J Vasc Surg 28:687–694PubMedCrossRef
go back to reference Boric M, Figueroa X, Donoso M, Paredes A, Poblete I, Huidobro-Toro J (1999) Rise in endothelium-derived NO after stimulation of rat perivascular sympathetic mesenteric nerves. Am J Physiol Heart Circ Physiol 277:H1027–H1035 Boric M, Figueroa X, Donoso M, Paredes A, Poblete I, Huidobro-Toro J (1999) Rise in endothelium-derived NO after stimulation of rat perivascular sympathetic mesenteric nerves. Am J Physiol Heart Circ Physiol 277:H1027–H1035
go back to reference Bruck H, Gössl M, Spitthöver R, Schäfers R, Kohnle M, Philipp T, Wenzel R (2001) The nitric oxide synthase inhibitor l-NMMA potentiates noradrenaline-induced vasoconstriction: effects of the alpha2-receptor antagonist yohimbine. J Hypertens 19(5):907–911PubMedCrossRef Bruck H, Gössl M, Spitthöver R, Schäfers R, Kohnle M, Philipp T, Wenzel R (2001) The nitric oxide synthase inhibitor l-NMMA potentiates noradrenaline-induced vasoconstriction: effects of the alpha2-receptor antagonist yohimbine. J Hypertens 19(5):907–911PubMedCrossRef
go back to reference Celermajer D, Sorensen K, Gooch V, Spiegelhalter D, Miller O, Sullivan I, Lloyd J, Deanfield J (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340(8828):1111–1115PubMedCrossRef Celermajer D, Sorensen K, Gooch V, Spiegelhalter D, Miller O, Sullivan I, Lloyd J, Deanfield J (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340(8828):1111–1115PubMedCrossRef
go back to reference Cracowski JL, Minson CT, Salvat-Melis M, Halliwill JR (2006) Methodological issues in the assessment of skin microvascular endothelial function in humans. Trends Pharmacol Sci 27:503–508PubMedCrossRef Cracowski JL, Minson CT, Salvat-Melis M, Halliwill JR (2006) Methodological issues in the assessment of skin microvascular endothelial function in humans. Trends Pharmacol Sci 27:503–508PubMedCrossRef
go back to reference De Fronzo R, Tobin J, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214–E223 De Fronzo R, Tobin J, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214–E223
go back to reference Elliott T, Cockcroft J, Groop P, Viberti G, Ritter J (1993) Inhibition of nitric oxide synthesis in forearm vasculature of insulin-dependent diabetic patients: blunted vasoconstriction in patients with microalbuminuria. Clin Sci 85(6):687–693PubMed Elliott T, Cockcroft J, Groop P, Viberti G, Ritter J (1993) Inhibition of nitric oxide synthesis in forearm vasculature of insulin-dependent diabetic patients: blunted vasoconstriction in patients with microalbuminuria. Clin Sci 85(6):687–693PubMed
go back to reference Forst T, Kunt T, Pohlmann T, Goitom K, Lobig M, Engelbach M, Beyer J, Pfutzer A (1998) Microvascular skin blood flow following the ingestion of 75 g glucose in healthy individuals. Exp Clin Endocrinol Diabetes 106:454–459PubMedCrossRef Forst T, Kunt T, Pohlmann T, Goitom K, Lobig M, Engelbach M, Beyer J, Pfutzer A (1998) Microvascular skin blood flow following the ingestion of 75 g glucose in healthy individuals. Exp Clin Endocrinol Diabetes 106:454–459PubMedCrossRef
go back to reference Halkin A, Benjamin N, Doktor H, Todd S, Viberti G, Ritter J (1991) Vascular responsiveness and cation exchange in insulin-dependent diabetes. Clin Sci 81(2):223–232PubMed Halkin A, Benjamin N, Doktor H, Todd S, Viberti G, Ritter J (1991) Vascular responsiveness and cation exchange in insulin-dependent diabetes. Clin Sci 81(2):223–232PubMed
go back to reference Johnstone M, Creager S, Scales K, Cusco J, Lee B, Creager M (1993) Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation 88:2510–2516PubMedCrossRef Johnstone M, Creager S, Scales K, Cusco J, Lee B, Creager M (1993) Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation 88:2510–2516PubMedCrossRef
go back to reference Katz A, Ekberg K, Johansson B, Wahren J (2001) Diminished skin blood flow in Type I diabetes: evidence for non-endothelium-dependent dysfunction. Clin Sci 101:59–64PubMedCrossRef Katz A, Ekberg K, Johansson B, Wahren J (2001) Diminished skin blood flow in Type I diabetes: evidence for non-endothelium-dependent dysfunction. Clin Sci 101:59–64PubMedCrossRef
go back to reference Khan F, Greene S, Elhadd T, Belch J (2000) Impaired skin microvascular function in children, adolescents, and young adults with type 1 diabetes. Diabetes Care 23(2):215–220PubMedCrossRef Khan F, Greene S, Elhadd T, Belch J (2000) Impaired skin microvascular function in children, adolescents, and young adults with type 1 diabetes. Diabetes Care 23(2):215–220PubMedCrossRef
go back to reference Lestradet H, Papoz L, Hellouin de Menibus C, Levavasseur F, Besse J, Billaud L, Battistelli F, Tric P, Lestradet F (1981) Long-term study of mortality and vascular complications in juvenile-onset (type 1) diabetes. Diabetes 30:175–179PubMedCrossRef Lestradet H, Papoz L, Hellouin de Menibus C, Levavasseur F, Besse J, Billaud L, Battistelli F, Tric P, Lestradet F (1981) Long-term study of mortality and vascular complications in juvenile-onset (type 1) diabetes. Diabetes 30:175–179PubMedCrossRef
go back to reference McNally P, Watt P, Rimmer T, Burden A, Hearnshaw J, Thurston H (1994) Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus. Clin Sci 87(1):31–36PubMed McNally P, Watt P, Rimmer T, Burden A, Hearnshaw J, Thurston H (1994) Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus. Clin Sci 87(1):31–36PubMed
go back to reference Oomen P, Kant G, Dullaart R, Reitsma W, Smit A (2002) Acute hyperglycemia and hyperinsulinemia enhance vasodilatation in type 1 diabetes mellitus without increasing capillary permeability and inducing endothelial dysfunction. Microvasc Res 63(1):1–9. doi:10.1006/mvre.2001.2347 PubMedCrossRef Oomen P, Kant G, Dullaart R, Reitsma W, Smit A (2002) Acute hyperglycemia and hyperinsulinemia enhance vasodilatation in type 1 diabetes mellitus without increasing capillary permeability and inducing endothelial dysfunction. Microvasc Res 63(1):1–9. doi:10.​1006/​mvre.​2001.​2347 PubMedCrossRef
go back to reference Smits P, Kapma J, Jacobs M, Lutterman J, Thien T (1993) Endothelium-dependent vascular relaxation in patients with type I diabetes. Diabetes 42(1):148–153PubMedCrossRef Smits P, Kapma J, Jacobs M, Lutterman J, Thien T (1993) Endothelium-dependent vascular relaxation in patients with type I diabetes. Diabetes 42(1):148–153PubMedCrossRef
go back to reference Steinberg H, Brechtel G, Johnson A, Fineberg N, Baron A (1994) Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 94:1172–1179PubMedCentralPubMedCrossRef Steinberg H, Brechtel G, Johnson A, Fineberg N, Baron A (1994) Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 94:1172–1179PubMedCentralPubMedCrossRef
go back to reference Tooke J (1995) Microvascular function in human diabetes. A physiological perspective. Diabetes 44:721–726PubMedCrossRef Tooke J (1995) Microvascular function in human diabetes. A physiological perspective. Diabetes 44:721–726PubMedCrossRef
go back to reference Veves A, Saoaf R, Donaghue V, Mullooly C, Kistler J, Giurini J, Horton E, Fielding R (1997) Aerobic exercise capacity remains normal despite impaired endothelial function in the micro- and macrocirculation of physically active IDDM patients. Diabetes 46(11):1846–1852PubMedCrossRef Veves A, Saoaf R, Donaghue V, Mullooly C, Kistler J, Giurini J, Horton E, Fielding R (1997) Aerobic exercise capacity remains normal despite impaired endothelial function in the micro- and macrocirculation of physically active IDDM patients. Diabetes 46(11):1846–1852PubMedCrossRef
Metadata
Title
Acute hyperglycaemia does not alter nitric oxide-mediated microvascular function in the skin of adolescents with type 1 diabetes
Authors
Louise H. Naylor
Norhaida M. Yusof
Nirubasini Paramalingam
Timothy W. Jones
Elizabeth A. Davis
Daniel J. Green
Publication date
01-02-2014
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Applied Physiology / Issue 2/2014
Print ISSN: 1439-6319
Electronic ISSN: 1439-6327
DOI
https://doi.org/10.1007/s00421-013-2785-6

Other articles of this Issue 2/2014

European Journal of Applied Physiology 2/2014 Go to the issue