Interleukin-6 enhances glucose-stimulated insulin secretion from pancreatic β-cells: Potential involvement of the PLC-IP3-dependent pathway

Toshinobu Suzuki, Junta Imai, Tetsuya Yamada, Yasushi Ishigaki, Keizo Kaneko, Kenji Uno, Yutaka Hasegawa, Hisamitsu Ishihara, Yoshitomo Oka, Hideki Katagiri

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

OBJECTIVE - Interleukin-6 (IL-6) has a significant impact on glucose metabolism. However, the effects of IL-6 on insulin secretion from pancreatic β-cells are controversial. Therefore, we analyzed IL-6 effects on pancreatic β-cell functions both in vivo and in vitro. RESEARCH DESIGN AND METHODS - First, to examine the effects of IL-6 on in vivo insulin secretion, we expressed IL-6 in the livers of mice using the adenoviral gene transfer system. In addition, using both MIN-6 cells, a murine β-cell line, and pancreatic islets isolated from mice, we analyzed the in vitro effects of IL-6 pretreatment on insulin secretion. Furthermore, using pharmacological inhibitors and small interfering RNAs, we studied the intracellular signaling pathway through which IL-6 may affect insulin secretion from MIN-6 cells. RESULTS - Hepatic IL-6 expression raised circulating IL-6 and improved glucose tolerance due to enhancement of glucose stimulated-insulin secretion (GSIS). In addition, in both isolated pancreatic islets and MIN-6 cells, 24-h pretreatment with IL-6 significantly enhanced GSIS. Furthermore, pretreatment of MIN-6 cells with phospholipase C (PLC) inhibitors with different mechanisms of action, U-73122 and neomycin, and knockdowns of the IL-6 receptor and PLC-β1, but not with a protein kinase A inhibitor, H-89, inhibited IL-6-induced enhancement of GSIS. An inositol triphosphate (IP3) receptor antagonist, Xestospondin C, also abrogated the GSIS enhancement induced by IL-6. CONCLUSIONS - The results obtained from both in vivo and in vitro experiments strongly suggest that IL-6 acts directly on pancreatic β-cells and enhances GSIS. The PLC-IP3-dependent pathway is likely to be involved in IL-6-mediated enhancements of GSIS.

Original languageEnglish
Pages (from-to)537-547
Number of pages11
JournalDiabetes
Volume60
Issue number2
DOIs
Publication statusPublished - 2011 Feb

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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