Effects of glucagon-like peptide-I on glucose turnover in rats

The influences of glucagon-like peptide-I-(7-36) amide (GLP-I; 15 mumol. kg-1.min-1) on glucose turnover were studied in freely moving Wistar rats. In fed rats, GLP-1 reduced plasma glucose (from 7.3 +/- 0.2 to 5.6 +/- 0.3 mmol/l; P = 0.017), increased plasma insulin (from 20 +/- 3 to 89 +/- 11 mU/l; P = 0.002), and reduced plasma glucagon (from 44 +/- 1 to 35 +/- 2 pg/ml; P = 0.009) and glucose appearance rate (Ra; from 3.9 +/- 0.2 to 1.7 +/- 0.7 micromol.min-1. 100 g-1 after 30 min; P = 0.049) without affecting glucose disappearance rate (Rd). The glucose clearance rate (MCR) was increased (P = 0.048). In 48-h-fasted rats, GLP-I reduced plasma glucose (from 5.0 +/- 0.2 to 4.4 +/- 0.3 mmol/l; P = 0.035) and increased plasma insulin (from 4 +/- 1 to 25 +/- 10 mU/l; P = 0.042) and plasma glucagon (from 43 +/- 3 to 61 +/- 7 pg/ml; P = 0.046). Ra and Rd were not significantly affected, although Ra was lower than Rd after 15-30 min (P = 0.005) and MCR was increased (P = 0.049). Thus GLP-I reduces Ra in fed rats and increases MCR in fed and fasted rats. The reduced Ra seems mediated by an increased insulin-to-glucagon ratio; the increased glucose clearance seems dependent on insulin and a peripheral effect of GLP-I.