Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term Insulin resistance
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Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term Insulin resistance. / Sjøberg, Kim Anker; Rattigan, Stephen; Jeppesen, Jacob Fuglsbjerg; Lundsgaard, Annemarie; Holst, Jens Juul; Kiens, Bente.
In: Journal of Physiology, Vol. 593, No. 9, 2015, p. 2185-2198.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 131460107