1979-P: GLP-1 Recruits Skeletal Muscle Microvasculature without Impacting Glucose Uptake or Protein Metabolism in Older Men during Postabsorptive Insulin Clamps

Abstract

Introduction: Ageing muscle is associated with impaired blood flow, “anabolic resistance” to dietary protein, and impaired glucose uptake - culminating in muscle atrophy and insulin resistance. Since GLP-1 has been shown to recruit muscle microvasculature, and due to the presence of its receptors in local tissue(s) (e.g., endothelium, myocytes) we hypothesized that GLP-1 infusions in older people, would positively impact muscle microcirculation, protein and/or glucose metabolism - in an insulin-independent fashion. Methods: We studied seven older men (∼70±1 y, mean±SEM) in a cross-over design. Baseline measures were taken (first 3 h) prior to insulin and glucose clamps where participants received co-infusions of octreotide, Vamin 14-EF (containing essential amino acids and dextrose) - with or without GLP-1, over the next 3 h. Four muscle biopsies were taken over 90-120 minute intervals. Muscle protein turnover was quantified via A-V balance, and direct incorporation of 13C6 phenylalanine via mass spectrometric techniques. Plasma GLP-1 and insulin were quantified via Milliplex Map, ELISA. Muscle microvascular flow was assessed via contrast enhanced ultrasound. Leg glucose uptake was determined via A-V balance. Results: GLP-1 increased microvascular flow in +GLP-1 vs. -GLP-1 conditions (increase vs. without GLP-1 infusion: 7.2±4.7 vs. 0.40±0.26-fold, p=0.009) while leg glucose uptake was unchanged. Muscle proteolysis (nb. no effects on synthesis) was equally suppressed vs. basal with GLP-1 (32.1±5.3 vs. 67.4±3.2 nmol.100 g leg-1.min-1, p<0.05) and without GLP-1 (32.77±6.1 vs. 57.9±5.1 nmol.100 g leg-1.min-1 p<0.05, respectively). Conclusion: GLP-1 recruits muscle microcirculation independent of insulin. A lack of impact of GLP-1 on muscle glucose uptake or protein metabolism, could reflect a requirement for fed-state insulin levels. GLP-1 may hold therapeutic value for muscle microvascular health. Disclosure H. Abdulla: None. B.E. Phillips: None. M.C. Limb: None. D.J. Wilkinson: None. T. Jandova: None. J. Cegielski: None. J.J. Bass: None. D. Rankin: None. J.S. Lewis: None. J. Williams: None. K. Smith: None. P.J. Atherton: None. I.R. Idris: None. Funding Medical Research Council UK; Arthritis Research UK