Fig 6. Proposed model for the inhibitory effect of prolonged Htr2b activation on GSIS in MIN6 cells.

MIN6 cells constitute a functional microserotoninergic system, with the ability to synthesis 5HT from its precursors (tryptophan or 5HTP), storage, degrade and release this monoamine. The extracellular 5HT may decrease GSIS through the activation of the Htr2b receptor, the most abundantly 5HT receptor expressed in MIN6 cells. Prolonged Htr2b activation is accompanied with calcium release from endoplasmic reticulum and its inhibitory effects on GSIS is likely the result of enhanced PGC1α/PPARy expression and mitochondrial dysfunction with decreased glucose-stimulated ATP synthesis.