Epoxyeicosatrienoic acids stimulate glucagon and insulin release from isolated rat pancreatic islets

Falck, John R.; Manna, Sukumar; Moltz, J. H.; Chacos, N.; Capdevila, Jorge H.

doi:10.1016/0006-291x(83)90843-4

Cited by 158 publications

(81 citation statements)

References 15 publications

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“…Our finding that EETs inhibit insulin secretion contrasts with a previous study showing that 5,6-EET increases insulin secretion from rat islets (17). In this study, however, 8,9-EET, 11,12-EET, and 14,15-EET increased glucagon secretion, but not insulin secretion.…”

Section: Discussioncontrasting

confidence: 99%

“…Similarly, different EET species also alter beta-cell function. Thus, 5,6-EET, but not 8,9-, 11,12-, or 14,15-EET, stimulates insulin secretion in isolated rat islets (17), and 8,9-, 11,12-, and 14,15-EET stimulate glucagon release from the same islets. Although AA and its metabolites play a role in GSIS, it is not understood how these metabolites are regulated in the beta-cell or how they might stimulate or impair insulin secretion.…”

mentioning

confidence: 80%

“…We used the EET concentrations (1 M) that were previously used in rat islet experiments (17). At basal glucose concentrations, the EET species did not alter insulin secretion (Fig.…”

Section: Eets Inhibit Gsis and Inhibiting Eet Actions Rescue The Redumentioning

confidence: 99%

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Diminished Acyl-CoA Synthetase Isoform 4 Activity in INS 832/13 Cells Reduces Cellular Epoxyeicosatrienoic Acid Levels and Results in Impaired Glucose-stimulated Insulin Secretion

Klett

Chen

Edin

et al. 2013

Journal of Biological Chemistry

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Background:The role of intracellular lipid metabolism as it relates to nutrient-coupled glucose-stimulated insulin secretion has not been fully elucidated. Results: Knockdown of acyl-CoA synthetase isoform 4 impairs glucose-stimulated insulin secretion caused by decreased cellular epoxyeicosatrienoic acids. Conclusion: Acyl-CoA synthetase 4 is required for optimal glucose-stimulated insulin secretion. Significance: Understanding the role of beta-cell lipid metabolism is needed to develop novel strategies to enhance insulin secretion.

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Section: Discussioncontrasting

confidence: 99%

mentioning

confidence: 80%

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Diminished Acyl-CoA Synthetase Isoform 4 Activity in INS 832/13 Cells Reduces Cellular Epoxyeicosatrienoic Acid Levels and Results in Impaired Glucose-stimulated Insulin Secretion

Klett

Chen

Edin

et al. 2013

Journal of Biological Chemistry

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“…AA can be metabolized by cyclooxygenase to prostaglandins and related compounds, by lipoxygenases to leukotrienes, and by cytochrome P-450 enzymes to epoxyeicosatrienoic acids (33). Cytochrome P-450 generated epoxyeicosatrienoic acids have been shown to play a role in insulin secretion (34). We have studied the effects of the cytochrome P-450 inhibitor methylbenzyl-1-aminobenzotriazole (MB-1-ABT) (35) on insulin secretion induced by glucose and RX871024 (Fig.…”

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confidence: 99%

Two Generations of Insulinotropic Imidazoline Compounds

et al. 2002

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The imidazoline RX871024 increased basal-and glucosestimulated insulin release in vitro and in vivo. The compound inhibited activity of ATP-sensitive K ؉ channels as well as voltage-gated K ؉ channels, which led to membrane depolarization, an increase in the cytosolic Ca 2؉ concentration ([Ca 2؉ ] i ), and insulin release. Importantly, RX871024 also enhanced the insulinotropic effect of glucose in cells with clamped [Ca 2؉ ] i but in the presence of high ATP and Ca 2؉ concentration inside the cell. We believe that the latter effect on insulin exocytosis was at least in part mediated by a rise in diacylglycerol, which then activated protein kinase C (PKC) and increased the generation of arachidonic acid (AA) metabolites. Activation of both the PKC and AA pathways resulted in potentiation of glucose effects on insulin secretion. Unlike RX871024, the novel imidazoline BL11282 did not block ATP-dependent K ؉ channels, but similarly to RX871024, it stimulated insulin secretion in depolarized or permeabilized islets. Accordingly, BL11282 did not influence glucose and insulin levels under basal conditions either in vitro or in vivo, but it markedly enhanced the insulinotropic effects of glucose. BL11282 restored the impaired insulin response to glucose in islets from spontaneously diabetic GK rats. We conclude that BL11282 belongs to a new class of insulinotropic compounds that demonstrate a strong glucose-dependent effect on insulin exocytosis. Diabetes 51 (Suppl. 3):S448 -S454, 2002 G lucose stimulates insulin secretion mainly by activation of two mechanisms: increasing the cytosolic Ca 2ϩ concentration ([Ca 2ϩ ] i ) (1) and directly promoting insulin exocytosis (2). It has been demonstrated that sulfonylureas increase insulin secretion by simulating the effect of glucose on [Ca 2ϩ ] i (3). However, recent data suggest that sulfonylureas also moderately enhance the direct effect of glucose on exocytosis (4,5). The direct insulinotropic effect of sulfonylureas, observed already at normal or moderately increased blood glucose concentrations, may provoke pronounced and prolonged hypoglycemia in patients treated with these drugs (6). Therefore, drugs that solely enhance the exocytotic component of the insulinotropic effect of glucose by influencing transport and fusion of insulin granules could provide a better alternative to sulfonylureas in treatment of type 2 diabetes. It has been shown that glucagon like peptide-1 (GLP-1), a peptide from the gut, shows a glucose-dependent insulinotropic effect and exerts a strong antidiabetic effect (7). However, the necessity of injecting this peptide during the treatment led to the idea to search for small organic compounds possessing glucose-dependent insulinotropic activity similar to GLP-1. Among those compounds, of special interest are novel imidazoline compounds (8,9).Phentolamine, an ␣-adrenergic blocking agent with an imidazoline ring, stimulated basal and glucose-induced insulin release in humans and animals (10 -12). These data were initially interpreted as an indicati...

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“…5,6-EET directly stimulates the release of insulin but has no effect on glucagon release. In contrast, 8,9-EET, 11,12-EET, and 14,15-EET increase glucagon release without affecting insulin secretion (56). Vasopressininduced glycogenolysis was mediated by EETs, in particular 14,15-EET, in isolated rat hepatocytes (57).…”

Section: Diabetesmentioning

confidence: 96%

The Role of Cytochrome P450 Epoxygenases, Soluble Epoxide Hydrolase, and Epoxyeicosatrienoic Acids in Metabolic Diseases

Chen

et al. 2016

Advances in Nutrition

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Metabolic diseases are associated with an increased risk of developing cardiovascular disease. The features comprising metabolic diseases include obesity, insulin resistance, hyperglycemia, hyperlipidemia, and hypertension. Recent evidence has emerged showcasing a role for cytochrome P450 epoxygenases, soluble epoxide hydrolase, and epoxyeicosatrienoic acids (EETs) in the development and progression of metabolic diseases. This review discusses the current knowledge related to the modulation of cytochrome P450 epoxygenases and soluble epoxide hydrolase to alter concentrations of biologically active EETs, resulting in effects on insulin resistance, lipid metabolism, obesity, and diabetes. Future areas of research to address current deficiencies in the understanding of these enzymes and their eicosanoid metabolites in various aspects of metabolic diseases are also discussed. Adv Nutr 2016;7:1122-8.

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Epoxyeicosatrienoic acids stimulate glucagon and insulin release from isolated rat pancreatic islets

Cited by 158 publications

References 15 publications

Diminished Acyl-CoA Synthetase Isoform 4 Activity in INS 832/13 Cells Reduces Cellular Epoxyeicosatrienoic Acid Levels and Results in Impaired Glucose-stimulated Insulin Secretion

Diminished Acyl-CoA Synthetase Isoform 4 Activity in INS 832/13 Cells Reduces Cellular Epoxyeicosatrienoic Acid Levels and Results in Impaired Glucose-stimulated Insulin Secretion

Two Generations of Insulinotropic Imidazoline Compounds

The Role of Cytochrome P450 Epoxygenases, Soluble Epoxide Hydrolase, and Epoxyeicosatrienoic Acids in Metabolic Diseases

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