TY - JOUR

T1 - Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term Insulin resistance

AU - Sjøberg, Kim Anker

AU - Rattigan, Stephen

AU - Jeppesen, Jacob Fuglsbjerg

AU - Lundsgaard, Annemarie

AU - Holst, Jens Juul

AU - Kiens, Bente

N1 - CURIS 2015 NEXS 110

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1113/JP270129

DO - 10.1113/JP270129

M3 - Journal article

C2 - 25688993

VL - 593

SP - 2185

EP - 2198

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - 9

ER -