Cytokines and nitric oxide in islet inflammation and diabetes. Proc Soc Exp Biol Med 1996 Jan;211(1):24-32
Date
01/01/1996Pubmed ID
8594615DOI
10.3181/00379727-211-43950dScopus ID
2-s2.0-0030030057 (requires institutional sign-in at Scopus site) 237 CitationsAbstract
Cytokines released by both T lymphocytes and activated macrophages, in particular interleukin-1 (IL-1), have been implicated as immunological effector molecules that both inhibit insulin secretion from the pancreatic beta cell and induce beta-cell destruction. Recent findings have demonstrated that production of the free radical nitric oxide (NO), resulting from the expression of the cytokine-inducible isoform of NO synthase (iNOS), mediates these deleterious effects. The cellular mechanism responsible for inhibition of beta-cell function and destruction by NO involves, in part, inactivation of enzymes specifically localized to the beta-cell mitochondria that contain iron- sulfur centers or clusters. Intraislet release of IL-1 also inhibits beta-cell function by this same cellular mechanism involving the overproduction of NO. In addition, the cytokine, IL-1, induces the co-expression of both iNOS and the cytokine-inducible isoform of cyclooxygenase, COX-2. The expression of COX-2 results in the overproduction of the proinflammatory prostaglandins and thromboxanes. Furthermore, NO produced by iNOS directly stimulates the activities of both constitutive and inducible isoforms of COX, further augmenting the overproduction of these proinflammatory mediators, NO and prostaglandins, which may be important in initiating or maintaining the inflammatory response and destruction of the beta cell associated with autoimmune diabetes.
Author List
McDaniel ML, Kwon G, Hill JR, Marshall CA, Corbett JAAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCytokines
Diabetes Mellitus, Type 1
Humans
Inflammation
Insulin
Interleukin-1
Islets of Langerhans
Nitric Oxide
Nitric Oxide Synthase
Prostaglandin-Endoperoxide Synthases
