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Loss of insulin-mediated microvascular perfusion in skeletal muscle is associated with the development of insulin resistance

St-Pierre, P., Genders, A.J., Keske, M.A., Richards, S.M. and Rattigan, S. 2010, Loss of insulin-mediated microvascular perfusion in skeletal muscle is associated with the development of insulin resistance, Diabetes, obesity and metabolism, vol. 12, no. 9, pp. 798-805, doi: 10.1111/j.1463-1326.2010.01235.x.

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Title Loss of insulin-mediated microvascular perfusion in skeletal muscle is associated with the development of insulin resistance
Author(s) St-Pierre, P.
Genders, A.J.
Keske, M.A.
Richards, S.M.
Rattigan, S.
Journal name Diabetes, obesity and metabolism
Volume number 12
Issue number 9
Start page 798
End page 805
Total pages 8
Publisher Wiley
Place of publication London, England
Publication date 2010
ISSN 1462-8902
1463-1326
Keyword(s) glucose metabolism
insulin delivery
insulin resistance
microvascular disease
Summary Aim: The aetiology of the development of type 2 diabetes remains unresolved. In the present study, we assessed whether an impairment of insulin-mediated microvascular perfusion occurs early in the onset of insulin resistance. Materials and methods: Hooded Wistar rats were fed either a normal diet (ND) or a high-fat diet (HFD) for 4 weeks. Anaesthetized animals were subjected to an isoglycaemic hyperinsulinaemic clamp (3 or 10 mU/min/kg × 2 h), and measurements were made of glucose infusion rate (GIR), hindleg glucose uptake, muscle glucose uptake by 2-deoxy-d-glucose (R′g), glucose appearance (Ra), glucose disappearance (Rd), femoral blood flow (FBF) and hindleg 1-methylxanthine disappearance (1-MXD, an index of microvascular perfusion). Results: Compared with ND-fed animal, HFD feeding led to a mild increase in fasting plasma glucose and plasma insulin, without an increase in total body weight. During the clamps, HFD rats showed an impairment of insulin-mediated action on GIR, hindleg glucose uptake, R′g, Ra, Rd and FBF, with a greater loss of insulin responsiveness at 3 mU/min/kg than at 10 mU/min/kg. The HFD also impaired insulin-mediated microvascular perfusion as assessed by 1-MXD. Interestingly, 1-MXD was the only measurement that remained unresponsive to the higher dose of 10 mU/min/kg insulin. Conclusions: We conclude that the early stage of insulin resistance is characterized by an impairment of the insulin-mediated microvascular responses in skeletal muscle. This is likely to cause greater whole body insulin resistance by limiting the delivery of hormones and nutrients to muscle.
Language eng
DOI 10.1111/j.1463-1326.2010.01235.x
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30051952

Document type: Journal Article
Collection: School of Medicine
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