Endocrine Abstracts

Background and aims: Although 95% of serotonin is produced in the periphery, its functions have been ignored until now. Recently it became clear that theserotonin system in the periphery regulates multiple physiological aspects independently of the brain-derived serotonin. In particular, peripheral serotonin playsa pivotal function in the regulation of glucose and lipid homeostasis by acting on different organs and cell types. Serotonin produced in pancreatic b- cellspromotes insulin secretion and during pregnancy also b-cell proliferation. Serotonin produced in intestine acts on the liver to promote gluconeogenesis and tosuppress hepatic glucose uptake, and on white adipocytes to promote lipolysis and to suppress glucose uptake, adiponectin production and insulin action. Serotonin produced directly in the adipocytes suppresses thermogenesis and glucose uptake in another functional type of fat – brown adipose tissue. Moreover, serotonin might act directly on muscle to promote glycolysis, and it promotes cytokine production in macrophages. With our study, we want to see how peripheral serotonin affects peripheral insulin resistance and obesity in rats.

Materials and methods: Serotonin is a crucial factor supporting pancreatic b-cell function, using the Tph1 inhibitor – LP533401 (peripheral serotonin inhibitor), in our experiments, aiming suppressing serotonin synthesis in intestinal enterochromaffin cells and in pancreatic b-cells of experimental animals. We used 30 Wistar rats separate in 2 groups- rats with obesityand healthy rats (control group). Each of this groups was separated in other 2 – one with daily intraperitoneal injection of LP533401 (0.2 mg/kg) and one without. In 4 weeks period we were tracking blood glucose level, insulin secretion and rats weight. Thedifferences in the mean values among the groups are greater than would be expected by chance; there is a statistically significant difference (P ≤ 0.001) using SPSS program.

Results: It was shown that after application of LP533401 the weight of the rats in obese groupdecreased by 35.4% (P < 0.05), and by 15.4% (P < 0.05) in the control group using LP544401 and no significant dynamic in the groups without daily intraperitoneal injection of LP533401. Theresearch also shows decreasing of insulin resistance by 35.8% (P < 0.05) in obese rats group using LP533401 compering with the results in the beginning of the study.

Conclusion: Using LP533401 inhibitor for treatment of obesity in male Wistar rats, LP533401 significantly reduces peripheral insulin resistance and further reducing body weight not only in the obese and diabetic rats group, but also in the control group.