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

Citation

St Pierre, P and Genders, AJ and Keske, MA and Richards, SM and Rattigan, S, Loss of insulin-mediated microvascular perfusion in skeletal muscle is associated with the development of insulin resistance , Diabetes Obesity & Metabolism, 12, (9) pp. 798-805. ISSN 1462-8902 (2010) [Refereed Article]

DOI: doi:10.1111/j.1463-1326.2010.01235.x

Abstract

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 Χ 2 h), and measurements were made of glucose infusion rate (GIR), hindleg glucose uptake, muscle glucose uptake by 2-deoxy-D-glucose (Rg), 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, Rg, 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.

Item Details

Item Type:Refereed Article
Keywords:glucose metabolism, insulin delivery, insulin resistance, microvascular disease
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Cardiology (incl. Cardiovascular Diseases)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Diabetes
Author:St Pierre, P (Mr Philippe St Pierre)
Author:Genders, AJ (Ms Amanda Genders)
Author:Keske, MA (Dr Michelle Keske)
Author:Richards, SM (Dr Stephen Richards)
Author:Rattigan, S (Professor Stephen Rattigan)
ID Code:64984
Year Published:2010
Web of Science® Times Cited:24
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-09-21
Last Modified:2011-10-03
Downloads:0

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