β-Cell Responses to Nitric Oxide

Broniowska, Katarzyna A.; Oleson, Bryndon J.; Corbett, John A.

doi:10.1016/b978-0-12-800174-5.00012-0

Cited by 38 publications

(29 citation statements)

References 87 publications

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“…This finding is consistent with IL-1␤ serving as a common link to alterations in islet function and mass in both T1DM and T2DM. Furthermore, if nitric oxide is removed from cells within the first 24 h of IL-1␤ exposure, mitochondrial metabolism and insulin secretion are restored (5). In this study, we found that voltagegated calcium channel activity is not different between control and IL-1␤-exposed cells, but the ability to increase intracellular calcium in response to a glucose challenge is diminished (Fig.…”

Section: Discussionsupporting

confidence: 51%

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IL-1β reciprocally regulates chemokine and insulin secretion in pancreatic β-cells via NF-κB

Burke

Stadler

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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Proinflammatory cytokines impact islet ␤-cell mass and function by altering the transcriptional activity within pancreatic ␤-cells, producing increases in intracellular nitric oxide abundance and the synthesis and secretion of immunomodulatory proteins such as chemokines. Herein, we report that IL-1␤, a major mediator of inflammatory responses associated with diabetes development, coordinately and reciprocally regulates chemokine and insulin secretion. We discovered that NF-B controls the increase in chemokine transcription and secretion as well as the decrease in both insulin secretion and proliferation in response to IL-1␤. Nitric oxide production, which is markedly elevated in pancreatic ␤-cells exposed to IL-1␤, is a negative regulator of both glucose-stimulated insulin secretion and glucose-induced increases in intracellular calcium levels. By contrast, the IL-1␤-mediated production of the chemokines CCL2 and CCL20 was not influenced by either nitric oxide levels or glucose concentration. Instead, the synthesis and secretion of CCL2 and CCL20 in response to IL-1␤ were dependent on NF-B transcriptional activity. We conclude that IL-1␤-induced transcriptional reprogramming via NF-B reciprocally regulates chemokine and insulin secretion while also negatively regulating ␤-cell proliferation. These findings are consistent with NF-B as a major regulatory node controlling inflammation-associated alterations in islet ␤-cell function and mass. chemokine; inflammation; insulin secretion; interleukin-1; nitric oxide THE PROGRESSION TO BOTH TYPE 1 (T1DM) and type 2 diabetes mellitus (T2DM) proceeds via immune cell-associated alterations in islet ␤-cell mass and function. Alterations in islet ␤-cell mass and function are two major determinants controlling the total amount of insulin produced and secreted in response to physiological stimuli (e.g., glucose). Proinflammatory cytokines such as IL-1␤ and IFN␥ contribute significantly to losses in islet ␤-cell viability and insulin secretion. Islet

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Section: Discussionsupporting

confidence: 51%

“…The active iNOS enzyme produces nitric oxide, a free radical signaling molecule that impacts numerous cellular functions (5,28,46). In pancreatic ␤-cells, nitric oxide influences insulin secretion, DNA damage and repair, and overall cellular viability.…”

mentioning

confidence: 99%

IL-1β reciprocally regulates chemokine and insulin secretion in pancreatic β-cells via NF-κB

Burke

Stadler

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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“…In pancreatic ␤ cells, NO has been shown to affect insulin secretion and cell survival. Excessive NO can induce apoptotic death of pancreatic ␤ cells [3,17]. Induction of the transcription factor Nrf2, which regulates a battery of antioxidant and cytoprotective genes, has been documented to suppress oxidative damage in pancreatic islets of iNOS-transgenic mice and restore insulin secretion from pancreatic ␤ cells [32].…”

Section: Discussionmentioning

confidence: 99%

Regulation of insulin sensitivity, insulin production, and pancreatic β cell survival by angiotensin-(1-7) in a rat model of streptozotocin-induced diabetes mellitus

Yang

et al. 2015

Peptides

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“…Among the possible mediators of insulin-induced increase in cell death are ROS and NO, which have been shown to be deleterious to β cell viability (Konishi et al 1997, Nakamura et al 2006, Hou et al 2008, Sampson et al 2010, Bedoya et al 2012, Broniowska et al 2014). Moreover, insulin was shown to increase ROS release in several cell types (Mahadev et al 2001, Goldstein et al 2005a,b, Biswas et al 2007, Guichard et al 2008, including RINm (rat) pancreatic β-cells (Sampson et al 2010).…”

Section: Insulin Increases Ros Production In Min6 Cellsmentioning

confidence: 99%

Prolonged insulin treatment sensitizes apoptosis pathways in pancreatic β cells

Bucris

Beck

Boura‐Halfon

et al. 2016

Journal of Endocrinology

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Insulin resistance results from impaired insulin signaling in target tissues that leads to increased levels of insulin required to control plasma glucose levels. The cycle of hyperglycemia and hyperinsulinemia eventually leads to pancreatic β cell deterioration and death by a mechanism that is yet unclear. Insulin induces ROS formation in several cell types. Furthermore, death of pancreatic β cells induced by oxidative stress could be potentiated by insulin. Here, we investigated the mechanism underlying this phenomenon. Experiments were done on pancreatic β cell lines (Min-6, RINm, INS-1), isolated mouse and human islets, and on cell lines derived from nonpancreatic sources. Insulin (100 nM) for 24 h selectively increased the production of ROS in pancreatic β cells and isolated pancreatic islets, but only slightly affected the expression of antioxidant enzymes. This was accompanied by a time-and dose-dependent decrease in cellular reducing power of pancreatic β cells induced by insulin and altered expression of several ER stress response elements including a significant increase in Trb3 and a slight increase in iNos. The effect on iNos did not increase NO levels. Insulin also potentiated the decrease in cellular reducing power induced by H 2 O 2 but not cytokines. Insulin decreased the expression of MCL-1, an antiapoptotic protein of the BCL family, and induced a modest yet significant increase in caspase 3/7 activity. In accord with these findings, inhibition of caspase activity eliminated the ability of insulin to increase cell death. We conclude that prolonged elevated levels of insulin may prime apoptosis and cell death-inducing mechanisms as a result of oxidative stress in pancreatic β cells.

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β-Cell Responses to Nitric Oxide

Cited by 38 publications

References 87 publications

IL-1β reciprocally regulates chemokine and insulin secretion in pancreatic β-cells via NF-κB

IL-1β reciprocally regulates chemokine and insulin secretion in pancreatic β-cells via NF-κB

Regulation of insulin sensitivity, insulin production, and pancreatic β cell survival by angiotensin-(1-7) in a rat model of streptozotocin-induced diabetes mellitus

Prolonged insulin treatment sensitizes apoptosis pathways in pancreatic β cells

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