title: The central role of calcium in the effects of cytokines on beta-cell function: implications for type 1 and type 2 diabetes.
abstract: The appropriate regulation of intracellular calcium is a requirement for proper cell function and survival. This review focuses on the effects of proinflammatory cytokines on calcium regulation in the insulin-producing pancreatic beta-cell and how normal stimulus-secretion coupling, organelle function, and overall beta-cell viability are impacted. Proinflammatory cytokines are increasingly thought to contribute to beta-cell dysfunction not only in type 1 diabetes (T1D), but also in the progression of type 2 diabetes (T2D). Cytokine-induced disruptions in calcium handling result in reduced insulin release in response to glucose stimulation. Cytokines can alter intracellular calcium levels by depleting calcium from the endoplasmic reticulum (ER) and by increasing calcium influx from the extracellular space. Depleting ER calcium leads to protein misfolding and activation of the ER stress response. Disrupting intracellular calcium may also affect organelles, including the mitochondria and the nucleus. As a chronic condition, cytokine-induced calcium disruptions may lead to beta-cell death in T1D and T2D, although possible protective effects are also discussed. Calcium is thus central to both normal and pathological cell processes. Because the tight regulation of intracellular calcium is crucial to homeostasis, measuring the dynamics of calcium may serve as a good indicator of overall beta-cell function.
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville, United States.
authors.forename: James W
authors.initials: JW
authors.lastname: Ramadan
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Steiner
authors.forename: Christina M
authors.initials: CM
authors.lastname: O'Neill
authors.forename: Craig S
authors.initials: CS
authors.lastname: Nunemaker
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism
chemical_list: D016207:Cytokines; D007328:Insulin; D005947:Glucose; D002118:Calcium