Intra- and extracellular 5-HT modulates insulin secretion in opposing directions.

(A–C) Diabetes mellitus and β-cell dysfunction in Tph1−/− mice aged 64 to 70 wk and rescue with 5-HTP. Glucose tolerance test with simultaneous blood glucose (A) and serum insulin (B) measurements. Glucose to insulin ratios (C) are significantly increased in Tph1−/− without 5-HTP treatment before and after the glucose load. *p<0.05; n = 8 (wt and Tph1−/− + 5-HTP) and n = 6 (Tph1−/−). (D) Pargyline induces hyperglycemia in wt mice. After a meal of 60 min, mice were treated with pargyline (75 mg kg−1) and blood glucose was measured immediately and after additional 60 min. *p<0.05; n = 6. (E) Pargyline treatment substantially elevated insulin secretion in wt mice. Mice were treated as described in (D). *p<0.05; n = 6. (F) Glucose tolerance test of Tph1−/− and wt mice with systemic 5-HT pre-treatment. *p<0.05; n = 6. (G) Extracellular 5-HT inhibits insulin secretion in MIN-6, INS-1, and RINm5F insulinoma cells. Cells were treated with 5-HT (500 µM) at the beginning of a 60 min secretion period. Insulin secretion is normalized to glucose-induced control cells. *p<0.05; n = 4. (H) Insulin secretion of RINm5F cells with or without glucose and 5-HTP (500 µM; 3 h) or pargyline (20 µM; 3 h). *p<0.05; n = 3. All data are presented as means ± SEM.