TY - JOUR
T1 - Interleukin-6 enhances glucose-stimulated insulin secretion from pancreatic β-cells
T2 - Potential involvement of the PLC-IP3-dependent pathway
AU - Suzuki, Toshinobu
AU - Imai, Junta
AU - Yamada, Tetsuya
AU - Ishigaki, Yasushi
AU - Kaneko, Keizo
AU - Uno, Kenji
AU - Hasegawa, Yutaka
AU - Ishihara, Hisamitsu
AU - Oka, Yoshitomo
AU - Katagiri, Hideki
N1 - Funding Information:
Most aspects of conducting research employing animals have parallels in clinical research. In the United States, there are stringent safeguards for the care and use of all animals which are set out by two regulatory agencies. The first is the Office of Laboratory Animal Welfare (OLAW) of the National Institutes of Health, whose guidelines are required to be followed in all research funded by NIH. OLAW guidelines serve as a basis for practices by institutional animal care and use committees (IACUC). The second is the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) whose accreditation is voluntarily sought by most research institutions sustaining animal research. Just as for humans, only well-treated animals will yield quality data. Once subject protection is factored into research methods, experimental and procedural decisions continue to be an act of balancing the positives and negatives of any action.
Funding Information:
Many mid-range nursing theories have also integrated biology into their frameworks. For example, the theory of unpleasant symptoms 16 incorporates physiological, psychological and situational factors. The physiologic figures prominently alongside the behavioral in the relatively new framework of psychoneuroimmunology 17,18 and the human response model. 19 Several editorials and position papers have maintained that physiologic research is an important aspect of nursing research, 20-22 although there are also opposing views with regard to physiologic research in animals. 1,2 Finally, the biologic is a prominent feature in the National Institute for Nursing Research (NINR) priorities. Indeed, no fewer than 15 of the approximately 185 RO1s and R29s currently funded by NINR include animal model systems, and NINR currently funds several pre- and postdoctoral National Research Service Awards employing animal studies.
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
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U2 - 10.2337/db10-0796
DO - 10.2337/db10-0796
M3 - Article
C2 - 21270264
AN - SCOPUS:79551584783
SN - 0012-1797
VL - 60
SP - 537
EP - 547
JO - Diabetes
JF - Diabetes
IS - 2
ER -
