Effects of GLP-1 on γ-aminobutyric acid and serotonin metabolism in synaptosomal fractions from rat hypothalamus and brain stem

Glucagons - like peptide-1 (7-36) amide (GLP-1) is the main product of the glucagon gene expression in intestinal L cells. GLP-1 is released from the intestine into the circulation in response to the ingestion of food and is the most potent stimulator of glucose-induced insulin secretion. GLP-1 receptors have also been detected in discrete areas of rat brain and intracerebro ventricular injection of GLP-1 has been shown to inhibit feeding in fasted rats.Methods and Materials: This study is an in vitro study. Used rats are male and their weight is 200 to 220 grams and each group has 7 rats. In this study HPLC techniques were employed to evaluate the effects of GLP-1 on monoamine metabolism in rat brain as a neuropeptide.Synaptosoms were prepared from homogenates of combined hypothalamus and brain stem from rats in each group. The synaptosomal pellets incubated for 15 minutes in ashaker bath at 37 C. The effect of GLP-1 on synaptosoms was tested by adding 50 μL of GLP-1 5x10 –7 M to the incubation medium. For this group a control group was prepared by adding normal saline instead of GLP-1. The data were analyzed by T- test. GLP-1 decreased levels of serotonin (5-HT) by 20% (P<0.05) after 15 minutes of incubation with combined hypothalamus and brain stem synaptosomes. Level of 5-hydroxyindolacetic acid (5-HIAA), the principal metabolite of 5-HT, and tryptophan, the amino acid precursor of 5-HT decreased by 21% and 37 %(P<0.05) respectively. γ-Aminobutyric acid (GABA) and its amino acid precursor glutamic acid (Glu) were both quantities at the same conditions as above, but a operculum derivatization HPLC technique was used. The increase levels of GABA (14%) and Glu(6%) by GLP-1 was not significant. The results suggest that decreased synaptosomal levels of 5-HT and 5-HIAA caused by GLP-1 are due to diminished availability of tryptophan by the neuropeptide.