Study characterizes insulin secretion in response to metabolic stress

The development of type 2 diabetes is linked to persistent inflammation as a consequence of metabolic stress. Prolonged exposure to the proinflammatory molecule IL-1β is associated with reduced insulin secretion by pancreatic β cells, while short-term exposure to IL-1β has been shown to increase insulin levels. Reducing IL-1 signaling in patients with type 2 diabetes has had mixed success in clinical studies, suggesting multiple effects of IL-1β in insulin secretion. A new study in JCI Insight reveals that IL-1 signaling is an important mediator of islet compensation to metabolic stress. Patrick MacDonald and colleagues at the University of Alberta determined that IL-1β amplifies insulin secretion in healthy human islets. Islets from obese individuals were particularly sensitive to IL-1β stimulation; however, islets from obese subjects with type 2 diabetes were not responsive to IL-1β. In mice, inhibition of IL-1 signaling resulted in symptoms of type 2 diabetes, including glucose intolerance and impaired insulin secretion in response to metabolic stress. Additionally, the authors determined that IL-1β directly promotes insulin secretion by enhancing release of insulin-containing granules. The results of this study demonstrate that IL-1R signaling is important for glucose homeostasis.

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TITLE:

Interleukin-1 signaling contributes to acute islet compensation

AUTHOR CONTACT:

Patrick MacDonald
University of Alberta
pmacdonald@ualberta.ca

View this article at: http://insight.jci.org/articles/view/86055?key=9b0bc8f92d7ef888af8e

JCI Insight is the newest publication from the American Society of Clinical Investigation, a nonprofit honor organization of physician-scientists. JCI Insight is dedicated to publishing a range of translational biomedical research with an emphasis on rigorous experimental methods and data reporting. All articles published in JCI Insight are freely available at the time of publication. For more information about JCI Insight and all of the latest articles go to http://www.insight.jci.org.