Divergent effects of epinephrine and prostaglandin E2 on glucose-induced insulin secretion from perifused rat islets

Zawalich, Walter S.; Zawalich, Kathleen C.; Yamazaki, Hiroyuki

doi:10.1016/j.metabol.2006.08.016

Cited by 12 publications

(9 citation statements)

References 36 publications

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“…Although the effect of selective COX‐2 inhibitors and that of the predominant product PGE 2 on insulin secretion was investigated decades ago, conflicting results were reported, ranging from an inhibitory to a nonadverse effect on GSIS (14–18). The discrepancy could be due to the different experimental conditions used as well as to the origin of the β cells tested such as HIT cells, or rat or human islets (21, 22, 49, 50).…”

Section: Discussionmentioning

confidence: 99%

“…However, differing results regarding the role of the prostaglandin E 2 (PGE 2 ), the most prevalent COX‐2 product, on insulin secretion were reported. Although a few studies showed that PGE 2 inhibited GSIS in HIT cells (18–20), others reported a lack of inhibitory effect on insulin secretion in rat (21, 22) and human islets (21, 23). Moreover, an antiapoptotic effect of PGE 2 and its precursor arachidonic acid in MIN6 and BRIN‐BD11 cells was suggested (24, 25).…”

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confidence: 99%

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The role of Cox‐2 and prostaglandin E ₂ receptor EP3 in pancreatic β‐cell death

Amior

Srivastava

Nano³

et al. 2019

FASEB j.

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Elevated levels of lipids, in particular saturated fatty acids, are known to be associated with type 2 diabetes (T2D) and to have a negative effect on β‐cell function and survival. We bring new evidence indicating that palmitate up‐regulates cyclooxygenase‐2 (COX‐2) expression levels in human islets and in MIN6 β cells, and that it is elevated in islets isolated from T2D donors. Both small interfering specific cyclooxygenase‐2 small interfering RNA (siRNA) or the COX‐2 inhibitor celecoxib significantly inhibited apoptosis induced by palmitate. Prostaglandin E2 (PGE2), the predominant product of COX‐2 enzymatic activity, activates membrane receptors, which are members of the GPCR‐family (EP1‐EP4). In the present study, elevated expression of the PGE2 receptor subtype 3 (EP3) receptor was observed in β cells exposed to palmitate and in islets from individuals with T2D. Down‐regulation of the pathway using EP3 siRNA or the specific L‐798, 106 antagonist markedly decreased the levels of palmitate‐induced apoptosis. Altogether, our data put forward the COX‐2‐PGE2‐EP3 pathway as one of the mediators of palmitate‐induced apoptosis in β‐cells.—Amior, L., Srivastava, R., Nano, R., Bertuzzi, F., Melloul, D. The role of Cox‐2 and prostaglandin E2 receptor EP3 in pancreatic β‐cell death. FASEB J. 33, 4975–4986 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The role of Cox‐2 and prostaglandin E ₂ receptor EP3 in pancreatic β‐cell death

Amior

Srivastava

Nano³

et al. 2019

FASEB j.

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“…The reasons for this inconsistency have not always been apparent, although important differences in study design have likely played important roles. Some of these differences include use of static incubations for 40 h (36) and exclusion of isobutylmethylxanthine from perifusions (42,43). These are relevant concerns, because although PGE 2 inhibits both first and second phase glucose-induced insulin secretion, it primarily inhibits first phase, which occurs within minutes of glucose stimulation.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2, Not Microsomal Prostaglandin E Synthase-1, Is the Mechanism for Interleukin-1β-induced Prostaglandin E2 Production and Inhibition of Insulin Secretion in Pancreatic Islets

Parazzoli

Harmon

Vallerie

et al. 2012

Journal of Biological Chemistry

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Background:The mechanism whereby IL-1␤ induces islet PGE 2 production and inhibition of insulin secretion is unclear. Results: Basal COX-2 protein levels are stimulated by IL-1␤; mPGES-1 levels are not. Conclusion: COX-2, not mPGES-1, is the final regulatory enzyme for PGE 2 production. Significance: COX-2, not mPGES-1, is the pharmacologic target to protect islet function from IL-1␤ in type 2 diabetes.

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“…EP1-4 can be distinguished by their signaling properties: EP1 couples to G q ; EP2 and EP4 couple to G S ; and EP3 primarily couples to G i proteins [16], including the pertussin toxin (PTx) insensitive inhibitory protein Gα Z [17]. The role of PGE 2 in GSIS has been widely studied and is primarily demonstrated as being inhibitory to GSIS in in vitro , ex vivo , and in vivo settings [13], [16], [18], [19], [20], [21], [22], [23], [24]; however, these inhibitory effects have not been consistently observed [25], [26], [27], [28], [29].…”

Section: Introductionmentioning

confidence: 99%

Opposing effects of prostaglandin E 2 receptors EP3 and EP4 on mouse and human β-cell survival and proliferation

Carboneau

Allan

Townsend

et al. 2017

Molecular Metabolism

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ObjectiveHyperglycemia and systemic inflammation, hallmarks of Type 2 Diabetes (T2D), can induce the production of the inflammatory signaling molecule Prostaglandin E2 (PGE2) in islets. The effects of PGE2 are mediated by its four receptors, E-Prostanoid Receptors 1-4 (EP1-4). EP3 and EP4 play opposing roles in many cell types due to signaling through different G proteins, Gi and GS, respectively. We previously found that EP3 and EP4 expression are reciprocally regulated by activation of the FoxM1 transcription factor, which promotes β-cell proliferation and survival. Our goal was to determine if EP3 and EP4 regulate β-cell proliferation and survival and, if so, to elucidate the downstream signaling mechanisms.Methodsβ-cell proliferation was assessed in mouse and human islets ex vivo treated with selective agonists and antagonists for EP3 (sulprostone and DG-041, respectively) and EP4 (CAY10598 and L-161,982, respectively). β-cell survival was measured in mouse and human islets treated with the EP3- and EP4-selective ligands in conjunction with a cytokine cocktail to induce cell death. Changes in gene expression and protein phosphorylation were analyzed in response to modulation of EP3 and EP4 activity in mouse islets.ResultsBlockade of EP3 enhanced β-cell proliferation in young, but not old, mouse islets in part through phospholipase C (PLC)-γ1 activity. Blocking EP3 also increased human β-cell proliferation. EP4 modulation had no effect on ex vivo proliferation alone. However, blockade of EP3 in combination with activation of EP4 enhanced human, but not mouse, β-cell proliferation. In both mouse and human islets, EP3 blockade or EP4 activation enhanced β-cell survival in the presence of cytokines. EP4 acts in a protein kinase A (PKA)-dependent manner to increase mouse β-cell survival. In addition, the positive effects of FoxM1 activation on β-cell survival are inhibited by EP3 and dependent on EP4 signaling.ConclusionsOur results identify EP3 and EP4 as novel regulators of β-cell proliferation and survival in mouse and human islets ex vivo.

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Divergent effects of epinephrine and prostaglandin E2 on glucose-induced insulin secretion from perifused rat islets

Cited by 12 publications

References 36 publications

The role of Cox‐2 and prostaglandin E ₂ receptor EP3 in pancreatic β‐cell death

The role of Cox‐2 and prostaglandin E ₂ receptor EP3 in pancreatic β‐cell death

Cyclooxygenase-2, Not Microsomal Prostaglandin E Synthase-1, Is the Mechanism for Interleukin-1β-induced Prostaglandin E2 Production and Inhibition of Insulin Secretion in Pancreatic Islets

Opposing effects of prostaglandin E 2 receptors EP3 and EP4 on mouse and human β-cell survival and proliferation

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Divergent effects of epinephrine and prostaglandin E2 on glucose-induced insulin secretion from perifused rat islets

Cited by 12 publications

References 36 publications

The role of Cox‐2 and prostaglandin E 2 receptor EP3 in pancreatic β‐cell death

The role of Cox‐2 and prostaglandin E 2 receptor EP3 in pancreatic β‐cell death

Cyclooxygenase-2, Not Microsomal Prostaglandin E Synthase-1, Is the Mechanism for Interleukin-1β-induced Prostaglandin E2 Production and Inhibition of Insulin Secretion in Pancreatic Islets

Opposing effects of prostaglandin E 2 receptors EP3 and EP4 on mouse and human β-cell survival and proliferation

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The role of Cox‐2 and prostaglandin E ₂ receptor EP3 in pancreatic β‐cell death

The role of Cox‐2 and prostaglandin E ₂ receptor EP3 in pancreatic β‐cell death