@article{10.1172/jci.insight.86055, author = {Catherine Hajmrle AND Nancy Smith AND Aliya F. Spigelman AND Xiaoqing Dai AND Laura Senior AND Austin Bautista AND Mourad Ferdaoussi AND Patrick E. MacDonald}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Interleukin-1 signaling contributes to acute islet compensation}, year = {2016}, month = {4}, volume = {1}, url = {https://insight.jci.org/articles/view/86055}, abstract = {IL-1β is a well-established inducer of both insulin resistance and impaired pancreatic islet function. Despite this, findings examining IL-1 receptor deficiency or antagonism in in vivo animal models, as well as in clinical studies of type 2 diabetic (T2D) patients, have led to conflicting results, suggesting that the actions of IL-1β on glycemic control may be pleiotropic in nature. In the present work, we find that the ability of IL-1β to amplify glucose-stimulated insulin secretion from human islets correlates with donor BMI. Islets from obese donors are sensitized to the insulinotropic effects of this cytokine, whereas the stimulatory effects of IL-1β are lost in islets from obese T2D patients, suggesting a role for IL-1 signaling in islet compensation. Indeed, mice deficient in IL-1 receptor type I become glucose intolerant more rapidly than their WT littermates and have impaired secretory responses during the acute stages of inflammatory and metabolic stress induced by LPS and high-fat diet, respectively. IL-1β directly enhances β cell insulin secretion by increasing granule docking and soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complex formation at the plasma membrane. Together, our study highlights the importance of IL-1β signaling in islet compensation to metabolic and inflammatory stress.}, number = {4}, doi = {10.1172/jci.insight.86055}, url = {https://doi.org/10.1172/jci.insight.86055}, }