The central role of calcium in the effects of cytokines on beta-cell function: Implications for type 1 and type 2 diabetes

Ramadan, James W.; Steiner, Stephen R.; O’Neill, Christina M.; Nunemaker, Craig S.

doi:10.1016/j.ceca.2011.08.005

Cited by 83 publications

(77 citation statements)

References 197 publications

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“…This effect is probably mediated by diacylglycerol production and protein kinase C activation (Welsh et al, 1989;Eizirik et al, 1995). The variability observed in these studies may reflect dosage dependence and the different cocktail combinations used in experiments (Ramadan et al, 2011).…”

Section: Endogenous Regulation Of Cav Channels In the Beta Cellmentioning

confidence: 91%

“…However, cytokine-induced changes in VDCC activity and insulin secretion were not apparent. Early studies observed that interleukin-1 could inhibit glucosestimulated calcium influx in rat islets (Wolf et al, 1989), but other studies showed the opposite effect (Ramadan et al, 2011). This effect is probably mediated by diacylglycerol production and protein kinase C activation (Welsh et al, 1989;Eizirik et al, 1995).…”

Section: Endogenous Regulation Of Cav Channels In the Beta Cellmentioning

confidence: 99%

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Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

et al. 2016

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Pancreatic beta cells, unique cells that secrete insulin in response to an increase in glucose levels, play a significant role in glucose homeostasis. Glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells has been extensively explored. In this mechanism, glucose enters the cells and subsequently the metabolic cycle. During this process, the ATP/ADP ratio increases, leading to ATP-sensitive potassium (K ATP ) channel closure, which initiates depolarization that is also dependent on the activity of TRP nonselective ion channels. Depolarization leads to the opening of voltage-gated Na 1 channels (Nav) and subsequently voltage-dependent Ca 21 channels (Cav).The increase in intracellular Ca 21 triggers the exocytosis of insulin-containing vesicles. Thus, electrical activity of pancreatic beta cells plays a central role in GSIS. Moreover, many growth factors, incretins, neurotransmitters, and hormones can modulate GSIS, and the channels that participate in GSIS are highly regulated. In this review, we focus on the principal ionic channels (K ATP , Nav, and Cav channels) involved in GSIS and how classic and new proteins, hormones, and drugs regulate it. Moreover, we also discuss advances on how metabolic disorders such as metabolic syndrome and diabetes mellitus change channel activity leading to changes in insulin secretion.

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Section: Endogenous Regulation Of Cav Channels In the Beta Cellmentioning

confidence: 91%

Section: Endogenous Regulation Of Cav Channels In the Beta Cellmentioning

confidence: 99%

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

et al. 2016

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“…There are several important reviews covering this topic (Hellman et al, 1992;Berggren et al, 1993;Henquin et al, 1998;Niki, 1999;Bergsten, 2002;Tengholm and Gylfe, 2009;Yamazaki et al, 2010;Ramadan et al, 2011). Our focus in this review will be on the particular function of the inositol phosphate Ins(1,4,5)P 3 .…”

Section: Synergymentioning

confidence: 99%

New Horizons in Cellular Regulation by Inositol Polyphosphates: Insights from the Pancreaticβ-Cell

Barker

Berggren

2013

Pharmacol Rev

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“…Similar disruptions to [Ca 2ϩ ] i oscillations have been observed in islets from a diabetic mouse model (16). As [Ca 2ϩ ] i regulates glucose-stimulated insulin secretion, altered [Ca 2ϩ ] i may partially mediate cytokine-induced changes in insulin secretion (17).…”

mentioning

confidence: 99%

Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cδ

Farnsworth

Walter

Hemmati

et al. 2016

Journal of Biological Chemistry

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Pro-inflammatory cytokines contribute to the decline in islet function during the development of diabetes. Cytokines can disrupt insulin secretion and calcium dynamics; however, the mechanisms underlying this are poorly understood. Connexin36 gap junctions coordinate glucose-induced calcium oscillations and pulsatile insulin secretion across the islet. Loss of gap junction coupling disrupts these dynamics, similar to that observed during the development of diabetes. This study investigates the mechanisms by which pro-inflammatory cytokines mediate gap junction coupling. Specifically, as cytokine-induced NO can activate PKC␦, we aimed to understand the role of PKC␦ in modulating cytokine-induced changes in gap junction coupling. Isolated mouse and human islets were treated with varying levels of a cytokine mixture containing TNF-␣, IL-1␤, and IFN-␥. Islet dysfunction was measured by insulin secretion, calcium dynamics, and gap junction coupling. Modulators of PKC␦ and NO were applied to determine their respective roles in modulating gap junction coupling. High levels of cytokines caused cell death and decreased insulin secretion. Low levels of cytokine treatment disrupted calcium dynamics and decreased gap junction coupling, in the absence of disruptions to insulin secretion. Decreases in gap junction coupling were dependent on NO-regulated PKC␦, and altered membrane organization of connexin36. This study defines several mechanisms underlying the disruption to gap junction coupling under conditions associated with the development of diabetes. These mechanisms will allow for greater understanding of islet dysfunction and suggest ways to ameliorate this dysfunction during the development of diabetes.Diabetes is characterized by a progressive decrease in function and mass of ␤-cells, which comprise the majority of cells in the islets of Langerhans (1). Pro-inflammatory cytokines have been implicated as mediators of ␤-cell death in both type 1 diabetes (T1D) 2 and type 2 diabetes (T2D) (2-4). However, pro-inflammatory cytokines also play a role in causing ␤-cell dysfunction early in disease progression (3, 5). In T1D, high levels of pro-inflammatory cytokines, including tumor necrosis factor-␣ (TNF-␣), interleukin-1␤ (IL-1␤), and interferon ␥ (IFN-␥), are released by immune cells, such as CD4 ϩ and CD8 ϩ T-cells and macrophages, which infiltrate the pancreas (3, 6). In T2D, adipocyte stress resulting from obesity can lead to secretion of low levels of circulating TNF-␣ from activated macrophages in adipose tissue; whereas elevated free fatty acids and/or hyperglycemia can also lead to local release of IL-1␤ in the islets (4, 7). Although the mechanisms of cytokine-induced cell death in diabetes are well characterized, cytokine-induced islet dysfunction is poorly understood.In vitro, the pro-inflammatory cytokines TNF-␣, IL-1␤, and IFN-␥ work synergistically (8) to induce islet dysfunction and disrupt insulin secretion (9, 10). The effect of pro-inflammatory cytokines on the ␤-cell is thought to be mediated in part by...

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The central role of calcium in the effects of cytokines on beta-cell function: Implications for type 1 and type 2 diabetes

Cited by 83 publications

References 197 publications

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

New Horizons in Cellular Regulation by Inositol Polyphosphates: Insights from the Pancreaticβ-Cell

Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cδ

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