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The mechanisms of control of glucagon secretion are largely debated. In particular, the paracrine role of somatostatin (SST) is unclear. We studied its role in the control of glucagon secretion by glucose and K channel blockers, using perifused islets and the in situ perfused pancreas. The involvement of SST was evaluated by comparing glucagon release of control tissue or tissue without paracrine influence of SST (pertussis toxin-treated islets, or islets or pancreas from mice). We show that removal of the paracrine influence of SST suppresses the ability of K channel blockers or K channel ablation to inhibit glucagon release, suggesting that in control islets, the glucagonostatic effect of K channel blockers/ablation is fully mediated by SST. By contrast, the glucagonostatic effect of glucose in control islets is mainly independent of SST for low glucose concentrations (0-7 mmol/L) but starts to involve SST for high concentrations of the sugar (15-30 mmol/L). This demonstrates that the glucagonostatic effect of glucose only partially depends on SST. Real-time quantitative PCR and pharmacological experiments indicate that the glucagonostatic effect of SST is mediated by two types of SST receptors, SSTR2 and SSTR3. These results suggest that alterations of the paracrine influence of SST will affect glucagon release.

Data from our cohort, one of the largest so far reported, add to the evidence that proinflammatory cytokines such as Interleukin-1, Interleukin-6, Interleukin-10 and tumor necrosis factor-α are important in SLE pathogenesis.

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