229-OR: GLP-1 Infusions during Postprandial Insulin Clamps Enhance Muscle Microvascular Flow, Glucose Uptake, and Protein Anabolism in Older Men

Introduction: Ageing skeletal muscle becomes insulin resistant and atrophic. This is largely due to a failure in sequestering of amino acids and glucose from dietary intake into muscle protein and glycogen. GLP-1 possesses pleiotropic multi-organ properties and its receptor is expressed and exert effects in muscle tissue(s) e.g., endothelium. We hypothesized GLP-1 infusion would enhance muscle glucose uptake and bolster the trophic effects of an anabolic stimulus i.e., feeding.

Methods: Eight men (71±1y) were studied in a cross-over trial. Basal measures were taken (first 3 h) prior to insulin (i.e., postprandial (fed-state)) and glucose (euglycaemic) clamps. Participants received I.V co-infusions of octreotide, Vamin 14-EF ±GLP-1. Four muscle biopsies were taken at 90-120 min intervals. Muscle protein turnover was quantified via A-V balance and direct incorporation of ¹³C₆ phenylalanine via mass spectrometric techniques. GLP-1 and insulin were measured using Milliplex Map, ELISA kits. Muscle microvascular blood flow (MBF) was assessed via contrast enhanced ultrasound. Glucose handling was assayed by infusion rates and leg A-V balance.

Results: GLP-1 (vs. -GLP-1 condition) augmented muscle protein synthesis (basal: 0.058±0.004%.h^-1 vs. fed: 0.102±0.005%.h^-1, p<0.01), net protein balance (p<0.0001 and p=0.03 vs. basal at 1.5h and 3h postprandial, respectively) and MBF (5±2 vs. 1.9±0.7 fold-change from basal respectively, p<0.01) - while increasing whole-body glucose uptake (AUC 17.0±1.7 vs. 11.4±1.8 mg.kg^-1.180 min^-1, p=0.02 with and without GLP, respectively). Muscle protein breakdown was equally suppressed with and without GLP-1. Leg glucose uptake was unchanged by GLP-1.

Conclusions: The beneficial effects of GLP-1 upon whole-body glycaemic control are seemingly independent of muscle under fed-conditions. The pro-anabolic effect of GLP-1 in ageing is striking and requires further clinical and mechanistic research.