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

journal contribution
posted on 2023-05-17, 03:13 authored by St Pierre, P, Genders, AJ, Michelle Keske, Stephen RichardsStephen Richards, Stephen RattiganStephen Rattigan
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 (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.

History

Publication title

Diabetes Obesity & Metabolism

Volume

12

Issue

9

Pagination

798-805

ISSN

1462-8902

Department/School

Menzies Institute for Medical Research

Publisher

Blackwell Publishing Ltd

Place of publication

9600 Garsington Rd, Oxford, England, Oxon, Ox4 2Dg

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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