期刊
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
卷 17, 期 4, 页码 314-321出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MED.0b013e32833bf6dc
关键词
adipocyte; caspase-1; cytokines; inflammasome; inflammation
资金
- NIH [AI 15614, CA 6934]
- JDRF [26-2008-893]
- Royal Netherlands Academy of Arts Sciences
Purpose of review To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1 beta. Recent findings Recent studies from animals, in-vitro cultures and clinical trials provide evidence that support a causative role for IL-1 beta as the primary agonist in the loss of beta-cell mass in type 2 diabetes. In vitro, IL-1 beta-mediated autoinflammatory process results in beta-cell death. The autoinflammation is driven by glucose, free fatty acids, leptin, and IL-1 beta itself. Caspase-1 is required for IL-1 beta activity and the release of free fatty acids from the adipocyte. An emerging hypothesis gains support from patients with type 2 diabetes in which an imbalance in the amount of IL-1 beta agonist activity versus the specific countering by the naturally occurring IL-1 receptor antagonist (IL-1Ra) determines the outcome of islet inflammation. An important confirmation comes from clinical trials. Blockade of IL-1 receptor with anakinra, the recombinant form of IL-1Ra, or neutralizing anti-IL-1 beta antibodies, provides proof-of-principle data that reducing IL-1 beta activity is sufficient for correcting dysfunctional beta-cell production of insulin in type 2 diabetes, including a possibility that suppression of IL-1 beta-mediated inflammation in the microenvironment of the islet allows for regeneration. Summary Monotherapy or add-on therapy targeting IL-1 beta in type 2 diabetes holds promise for long-term benefits in glycemic control and possibly reducing cardiovascular events.
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