Intra- and extracellular 5-HT modulates insulin secretion in opposing directions. PaulmannNils GrohmannMaik VoigtJörg-Peter BertBettina VowinckelJakob BaderMichael SkelinMaša JevšekMarko FinkHeidrun RupnikMarjan J. WaltherDiego 2009 <p>(A–C) Diabetes mellitus and β-cell dysfunction in <i>Tph1</i>−/− 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 <i>Tph1</i>−/− without 5-HTP treatment before and after the glucose load. *<i>p</i><0.05; <i>n</i> = 8 (wt and <i>Tph1</i>−/− + 5-HTP) and <i>n</i> = 6 (<i>Tph1</i>−/−). (D) Pargyline induces hyperglycemia in wt mice. After a meal of 60 min, mice were treated with pargyline (75 mg kg<sup>−1</sup>) and blood glucose was measured immediately and after additional 60 min. *<i>p</i><0.05; <i>n</i> = 6. (E) Pargyline treatment substantially elevated insulin secretion in wt mice. Mice were treated as described in (D). *<i>p</i><0.05; <i>n</i> = 6. (F) Glucose tolerance test of <i>Tph1</i>−/− and wt mice with systemic 5-HT pre-treatment. *<i>p</i><0.05; <i>n</i> = 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. *<i>p</i><0.05; <i>n</i> = 4. (H) Insulin secretion of RINm5F cells with or without glucose and 5-HTP (500 µM; 3 h) or pargyline (20 µM; 3 h). *<i>p</i><0.05; <i>n</i> = 3. All data are presented as means ± SEM.</p>