Impaired insulin secretion in pancreatic β-cells lacking the sphingosine-1-phosphate_1 receptor

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Pancreatic islet beta cells secrete insulin in response to glucouse stimulation. To elucidate how S1P_1 is involved in such insulin secretion, whole process from insulin generation to its secretion through S1P_1 on pancreatic beta cell was investigated. First, Morphological study of pancreatic islet and islet hormones contents of S1P_1 knocked out mouse (S1P_1KO) were measured compared to Control litter mate.Results 1. Morphological analysis of S1P_1KO showed no clear difference compared to Control. Immunohistochemistry using antibody for Insulin, Glukagon, Somatostatin and IPAA showed similar staining pattern in both groups. 2. Beta cell organelle showed similar morphology using electronic microscopy in both groups. Also, the number of docking beta cell granules to the plasma membrane reached no statistic difference. 3. S1P_1 phosphorylates ERK kinase in response to its ligand, sphingosin-1-phosphate (S1P). Western brotting analysis using phosph-ERK anti-body by S1P stimulatin revealed weaker phosphrylation of ERK in S1P_1KO islet than in Control. 4. S1P_1 receptor belongs to the family of G protein coupled receptor and couples Gi protein exclusively. S1P_1KO islet showed higher cAMP production in response to GLP-1 stimulation than Control islet cAMP specific ELISA.Conclusions 1. S1P_1 had no apparent effect for islet mass and ratio of islet cell composition. 2. S1P_1 in pancreatic beta cell coupled Gi protein.