Interleukin-6 Enhances Glucose-Stimulated Insulin Secretion From Pancreatic β-Cells

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-β 1 , but not with a protein kinase A inhibitor, H-89, inhibited IL-6–induced enhancement of GSIS. An inositol triphosphate (IP 3 ) 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-IP 3 –dependent pathway is likely to be involved in IL-6-mediated enhancements of GSIS.

Cardiotrophin 1 protects beta cells from apoptosis and prevents streptozotocin-induced diabetes in a mouse model

“…The activation of PLC has been implicated in the mechanism of calcium release and activation of other secondary effectors that mediate insulin secretion [26]. In addition, it has been demonstrated that IL-6 activates the PLC pathway in different cell types [22], including beta cells [25]. Concordant with these results, Suzuki et al [25] showed that different PLC inhibitors were able to block insulin secretion mediated by IL-6.…”

“…In addition, it has been demonstrated that IL-6 activates the PLC pathway in different cell types [22], including beta cells [25]. Concordant with these results, Suzuki et al [25] showed that different PLC inhibitors were able to block insulin secretion mediated by IL-6. Therefore, we tested the effect of treating MIN6B1 cells with the PLC inhibitor neomycin (10 μmol/l) (Fig.…”

“…CT-1 enhances glucose-stimulated insulin secretion from MIN6B1 cells through the activation of the PLC pathway Recent studies have shown that co-family member IL-6 can induce insulin secretion in MIN6 cells [24,25]. We now show that in the presence of high glucose, CT-1 treatment likewise stimulates insulin secretion from MIN6B1 cells (Fig.…”

Physiological concentrations of interleukin-6 directly promote insulin secretion, signal transduction, nitric oxide release, and redox status in a clonal pancreatic β-cell line and mouse islets

“…2). Higher concentrations of IL6 (600-1200 pg/ml) were recently reported to significantly increase insulin secretion from mouse islets and also MIN6 b-cells (Suzuki et al 2011), but the physiological significance of such a high-concentration finding remains to be established. The authors speculate that IL6 b-cell action is of physiological importance following termination of exercise in vivo, when insulin secretion and subsequent action at the level of skeletal muscle will aid in recovery mechanisms.…”

Exploration of the Relationship between Adipocytokines, Tradition Risk Markers, Nontraditional Risk Markers and Anthropometric Measurements in T2DM Patients

“…The list of adipokines known to regulate glucose homeostasis increases every year, with reports identifying MCP-1 [73], IL-6 [74], IL-1β (Interleukin-1 beta) [75], adipolin [76], omentin [77] and even DPP4 (Dipeptidyle Peptidase 4) [78] have been identified as fat-secreted molecules that can regulate either insulin secretion or action. This list will no doubt continue to increase and the prospect of adipokines providing a defining link between obesity and type 2 diabetes remains a tantalizing possibility.…”