Premilovac, D and Bradley, EA and Ng, HLH and Richards, SM and Rattigan, S and Keske, MA, Muscle insulin resistance resulting from impaired microvascular insulin sensitivity in Sprague Dawley rats, Cardiovascular Research, 98, (1) pp. 28-36. ISSN 0008-6363 (2013) [Refereed Article]
Copyright 2013 The Author
Aims: Enhanced microvascular perfusion of skeletal muscle is important for nutrient exchange and contributes ~40 insulin-mediated muscle glucose disposal. High fat-fed (36 fat wt./wt.) rats are a commonly used model of insulin-resistance that exhibit impairment of insulin-mediated microvascular recruitment and muscle glucose uptake, which is accompanied by myocyte insulin-resistance. Distinguishing the contribution of impaired microvascular recruitment and impaired insulin action in the myocyte to decreased muscle glucose uptake in these high-fat models is difficult. It is unclear whether microvascular and myocyte insulin-resistance develop simultaneously. To assess this, we used a rat diet model with a moderate increase (two-fold) in dietary fat.
Methods and results: Sprague Dawley rats fed normal (4.8 fat wt./wt., 5FD) or high (9.0 fat wt./wt., 9FD) fat diets for 4 weeks were subject to euglycaemic hyperinsulinemic clamp (10 mU/min/kg insulin or saline) or isolated hindlimb perfusion (1.5 or 15 nM insulin or saline). Body weight, epididymal fat mass, and fasting plasma glucose were unaffected by diet. Fasting plasma insulin and non-esterified fatty acid concentrations were significantly elevated in 9FD. Glucose infusion rate and muscle glucose uptake were significantly impaired during insulin clamps in 9FD. Insulin-stimulated microvascular recruitment was significantly blunted in 9FD. Insulin-mediated muscle glucose uptake between 5FD and 9FD were not different during hindlimb perfusion.
Conclusions: Impaired insulin-mediated muscle glucose uptake in vivo can be the direct result of reduced microvascular blood flow responses to insulin, and can result from small (two-fold) increases in dietary fat. Thus, microvascular insulin-resistance can occur independently to the development of myocyte insulin-resistance.
|Item Type:||Refereed Article|
|Keywords:||insulin resistance, microcirculation, high fat diet, skeletal muscle glucose uptake|
|Research Division:||Medical and Health Sciences|
|Research Group:||Clinical Sciences|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Author:||Premilovac, D (Dr Dino Premilovac)|
|Author:||Bradley, EA (Miss Eloise Bradley)|
|Author:||Ng, HLH (Miss Huei Ng)|
|Author:||Richards, SM (Dr Stephen Richards)|
|Author:||Rattigan, S (Professor Stephen Rattigan)|
|Author:||Keske, MA (Dr Michelle Keske)|
|Web of Science® Times Cited:||16|
|Deposited By:||Menzies Institute for Medical Research|
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