Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term Insulin resistance

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Acute infusion of glucagon-like-peptide-1 (GLP-1) has potent effects on blood flow distribution through the microcirculation in healthy humans and rats. High fat diet induces impairments in insulin-mediated microvascular recruitment (MVR) and muscle glucose uptake, and here we examined whether this could be reversed by GLP-1. Using contrast-enhanced ultrasound, microvascular recruitment was assessed by continuous real-time imaging of gas-filled microbubbles in the microcirculation after acute (5 days) and prolonged (8 weeks) high fat diet (HF) induced insulin resistance in rats. An euglycemic hyperinsulinemic clamp (3 mU·min(-1) ·kg(-1) ) with or without a co-infusion of GLP-1 (100 pmol·l(-1) ) was performed in anaesthetized rats. Consumption of the HF diet attenuated the insulin-mediated MVR in both 5 days and 8 weeks HF interventions which was associated with a 50% reduction in insulin-mediated glucose uptake compared to controls. Acute administration of GLP-1 restored normal microvascular response by increasing the MVR after both 5 days and 8 weeks HF intervention (P<0.05). This effect of GLP-1 was associated with a restoration of both whole body insulin sensitivity and increased insulin-mediated glucose uptake in skeletal muscle by 90% (P<0.05) after 5 days HF diet but not after 8 weeks. The present study demonstrates that GLP-1 increases MVR in rat skeletal muscle and can reverse early stages of HF diet induced insulin resistance in vivo. This article is protected by copyright. All rights reserved.

TidsskriftJournal of Physiology
Udgave nummer9
Sider (fra-til)2185-2198
Antal sider14
StatusUdgivet - 2015

Bibliografisk note

CURIS 2015 NEXS 110

ID: 131460107