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Action of Glucagon and Glucagon-Like Peptide-1-(7-36) Amide on Lipolysis in Human Subcutaneous Adipose Tissue and Skeletal Muscle in Vivo¹

Department of Endocrinology (P.A., J.B., E.H.-T.), Huddinge University Hospital, CME M63, SE-141 86 Stockholm, Sweden; and Department of Endocrinology (E.B.), Nutrition, and Metabolism, Reims University Hospital, 51092 Reims Cedex, France

Address all correspondence and requests for reprints to: Eva Hagström-Toft, Center of Metabolism and Endocrinology, M63, Huddinge University Hospital, SE-141 86 Stockholm, Sweden. E-mail: eva.toft{at}mkdiv.hs.sll.se

In vitro and animal studies have shown that glucagon and glucagon-like peptide-1 (GLP-1)-(7-36) amide may participate in the regulation of lipolysis. However, results on human subjects in vivo are inconclusive. To avoid confounding effects, such as changes in insulin secretion when perfusing hormones iv, we used the in situ microdialysis to analyze the impact of human glucagon and GLP-1 on lipolysis rates and local blood flow. Nine healthy volunteers were given an 80-min local perfusion of each hormone (10^-6 mol/L), both in skeletal muscle (gastrocnemius) and in sc abdominal adipose tissue, after a basal period with perfusion of Ringer’s solution. Variations in the lipolysis rate and blood flow, respectively, were assessed by measuring of the dialysate glycerol content and the ethanol ratio (outgoing-to-ingoing ethanol concentration). The in vitro relative recovery of the microdialysis probes was 5.2 ± 1.2%. No significant effects of either GLP-1 or glucagon on either lipolysis rate or blood flow were detected in muscle or adipose tissue. Isoprenaline (10^-6 mol/L), which was perfused after glucagon or GLP-1 in the same catheters, significantly increased the lipolysis rate (a 249% increase of dialysate glycerol in adipose tissue and a 72% increase in skeletal muscle). Furthermore, isoprenaline, but not glucagon or GLP-1, stimulated lipolysis in vitro in isolated human sc adipose tissue. We conclude that neither glucagon nor GLP-1 affect the lipolysis rate of human sc adipose tissue or skeletal muscle.

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