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The Journal of physiology

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


PMID 25688993

Abstract

Acute glucagon-like peptide-1 (GLP-1) infusion reversed the high fat diet-induced microvascular insulin resistance that occurred after both 5xa0days and 8xa0weeks of a high fat diet intervention. When GLP-1 was co-infused with insulin it had overt effects on whole body insulin sensitivity as well as insulin-mediated skeletal muscle glucose uptake after 5xa0days of a high fat diet, but not after 8xa0weeks of high fat diet intervention. Acute GLP-1 infusion did not have an additive effect to that of insulin on microvascular recruitment or skeletal muscle glucose uptake in the control group. Here we demonstrate that GLP-1 potently increases the microvascular recruitment in rat skeletal muscle but does not increase glucose uptake in the fasting state. Thus, like insulin, GLP-1 increased the microvascular recruitment but unlike insulin, GLP-1 had no direct effect on skeletal muscle glucose uptake. Acute infusion of glucagon-like peptide-1 (GLP-1) has potent effects on blood flow distribution through the microcirculation in healthy humans and rats. A 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 (5xa0days) and prolonged (8xa0weeks) high fat diet (HF)-induced insulin resistance in rats. A euglycaemic hyperinsulinaemic clamp (3xa0mUxa0min(-1) xa0kg(-1) ), with or without a co-infusion of GLP-1 (100xa0pmolxa0l(-1) ), was performed in anaesthetized rats. Consumption of HF attenuated the insulin-mediated MVR in both 5xa0day and 8xa0week HF interventions which was associated with a 50% reduction in insulin-mediated glucose uptake compared to controls. Acute administration of GLP-1 restored the normal microvascular response by increasing the MVR after both 5xa0days and 8xa0weeks of HF intervention (Pxa0