Table 1.

Effects of extracellular S1P in beta-cells and islets in the absence or presence of proinflammatory cytokines or FFAs. The summary is based mainly on data gained in rat and mouse beta-cells and islets. Details are discussed in Section 7.1 and Section 8.1. Ref: References to the studies.

Conditions	Effects	Ref.
Extracellular S1P alone	Nontoxic nM-5 µM < 24 h >5 µM inhibition of cell viability and GSIS >5 µM induction of Caspase-3 activation > 5µM inhibition of proliferation 5 µM weak induction of NFκB nM no induction of iNOS and NO Increase in cAMP No effect on ATP content Insulin secretion stimulation at 3 mM Glc Potentiation of GSIS (<5 µM) HDL-mediated inhibition of TUNEL staining after IL-1β or HG (mouse and human islets) S1P receptors specific (major role of S1P2 and S1P3) (MIN6, mouse islets; INS1, rat islets)	[25,26,30,105] [26,30] [26,30,105] [26,30] [30] [105] [30] [30] [30] [24,26,27,30] [141] [26,106,142]
Extracellular S1P and proinflammatory cytokines	Prevention of caspase-3 activation (INS1E) Decrease in TUNEL staining (INS1, rat islets) Inhibition of apoptosis (MIN6) Prevention of cytochrome c release (INS1) Prevention of viability loss (INS1E) Partial protection from proliferation inhibition (INS1E) No additive effect on NFκB (INS1E) No additive effect on iNOS and NO (INS1) S1P2 and S1P3-mediated effects (MIN6, mouse islets, INS1, rat islets) PKC-mediated effects (INS1)	[30,105] [105] [26] [105] [30] [30] [30] [105] [26,105] [142] [106,142]
Extracellular S1P and FFAs	Prevention of PA-mediated apoptosis (double staining with annexin V and propidium iodide, caspase-3 activation, TUNEL staining) (INS1, MIN6, mouse islets) Prevention of PA-mediated cell death (PI) (MIN6)	[26,28] [28]