Arachidonic acid-induced insulin secretion from rat islets of Langerhans is not mediated by protein phosphorylation

Basudev, Harsha; Jones, Peter M.; Persaud, Shanta J.; Howell, S. L.

doi:10.1016/0303-7207(93)90272-l

Cited by 14 publications

(7 citation statements)

References 30 publications

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“…It has been recently shown that the mass of the a-PKC isoform at the plasma membrane of HIT cells is increased by Ca 2+ (41) and that of the a-and (3-PKC isoforms is downregulated by a phorbol ester, together with a corresponding abolition of the cholinergic potentiation of insulin secretion in MIN 6 cells (42). The present results suggest that palmitate might activate the same or other isoforms belonging to the calcium-and/or diacylglycerol-dependent PKC families (36).…”

Section: Discussionmentioning

confidence: 55%

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Stimulation of Islet Protein Kinase C Translocation by Palmitate Requires Metabolism of the Fatty Acid

Garnica

Qiu-Yue²,

Giné³

et al. 1997

Diabetes

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The secretory, metabolic, and signaling aspects of glucose/palmitate interaction on beta-cell function have been studied on rat islets. Palmitate potentiated the glucose-induced insulin response of perifused islets at suprathreshold (>3 mmol/l) sugar concentrations. This potentiating effect could be suppressed by 8-bromo-cGMP, which also blocks palmitate metabolism. Palmitate did not modify glucose utilization, but it slightly reduced glucose oxidation and concomitantly increased lactate production. The very low rate of palmitate oxidation (80-fold lower than that of 20 mmol/l glucose) might explain its lack of effect on glycolysis and hence that the glucose/fatty acid cycle is inoperative in islet cells. However, glucose determines the metabolic fate of exogenous palmitate, which is mainly diverted toward lipid synthesis at high sugar concentrations and might then generate lipid messengers for cell signaling. Palmitate did not increase glucose-induced production of inositol-1,4,5-trisphosphate, but it stimulated the translocation of protein kinase C activity from a cytosolic to a particulate fraction at 20 but not at 3 mmol/l glucose. This increased translocation was partially or completely blocked by hydroxycitrate or 8-bromo-cGMP, respectively, which are agents interfering with palmitate metabolism (inhibiting lipid synthesis). The metabolic interaction between glucose and palmitate might generate lipid messengers (diacylglycerol, phosphatidylserine) necessary for the activation of islet protein kinase C, which would in turn result in a potentiation of glucose-induced insulin secretion.

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Section: Discussionmentioning

confidence: 55%

“…First, it is known that saturated fatty acids (palmitate), in contrast to the cis-unsaturated species, do not directly stimulate purified islet PKC activity (36). Second, palmitate stimulation of islet PKC translocation occurred at 20 mmol/1 but not at 3 mmol/1 glucose.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Islet Protein Kinase C Translocation by Palmitate Requires Metabolism of the Fatty Acid

Garnica

Qiu-Yue²,

Giné³

et al. 1997

Diabetes

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“…However, they do not suggest that PKC is of major importance for the effects of palmitate on insulin release. Finally, palmitate did not stimulate PKC in islet cells (61) nor cause PKC translocation in HIT cells (21). Taken together, these results indicate that activation of PKC is not the mediator of the potentiation of insulin release by palmitate.…”

Section: Discussionmentioning

confidence: 98%

Mechanisms of the Stimulation of Insulin Release by Saturated Fatty Acids: A Study of Palmitate Effects in Mouse β-cells

Warnotte¹,

Gilon²,

Nenquin³

et al. 1994

Diabetes

172

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The mechanisms by which fatty acids increase insulin release are not known. In this study, mouse islets were used as a model and palmitate as a reference compound to study in vitro how saturated fatty acids influence pancreatic beta-cells. Palmitate (625 microM) was bound to albumin. It did not affect basal insulin release (3 mM glucose) but increased the release induced by 10-15 mM glucose. This effect was dependent on the concentration of free rather than total palmitate. It was reversible and abolished by epinephrine, diazoxide, nimodipine, or omission of extracellular Ca. Bromopalmitate and methyl palmoxirate, two inhibitors of fatty acid oxidation, were ineffective alone, and only bromopalmitate partially inhibited the effects of palmitate on insulin release. The increase in insulin release produced by palmitate could not be ascribed to a blockade of ATP-sensitive K(+)-channels because the fatty acid only barely decreased 86Rb efflux and did not depolarize beta-cells in 3 mM glucose. The small effect on 86Rb efflux might be attributed to a slight rise in the ATP/ADP ratio. No such rise occurred when palmitate was tested in 15 mM glucose, and the fatty acid consistently accelerated 86Rb efflux under these conditions. Measurements of beta-cell membrane potential (intracellular microelectrodes) and of free cytoplasmic calcium (Cai2+) in beta-cells (Fura 2 technique) showed that palmitate increases Ca2+ influx; it also caused a very small mobilization of intracellular Ca. The persistence of this stimulation of Ca2+ influx in the presence of diazoxide and high K+ suggests that palmitate might act on Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Since the secretory responses of islets to activation of PKC with PMA or to stimulation of Ca 2+ influx with 25 m m KCl were unchanged by 3‐MC‐pretreatment, attention is clearly focused on the possible effects of 3‐MC‐pretreatment on the modulation of arachidonic acid metabolism. Inhibition of both the cyclo‐oxygenase and lipoxygenase pathways of arachidonic acid metabolism does not result in complete inhibition of arachidonic acid‐stimulated insulin release (Basudev et al , 1993). Arachidonic acid metabolism by cytochrome P450 isoforms, including CYP1A and CYP4A families, via the epoxygenase pathway produces a range of cis ‐epoxyeicosatrienoic acids (EETs) and derivatives (Capdevila et al , 1981; 1983; Morrison & Pascoe, 1981; Oliw & Oates, 1981).…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P450 1A‐like proteins expressed in the islets of Langerhans and altered pancreatic β‐cell secretory responsiveness

Clarke¹,

Flatt²,

Barnett³

1997

British J Pharmacology

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1 The cytochrome P450 (CYP) mixed-function oxidase system is widely distributed in body tissues and plays a key role in the metabolism of endogenous and exogenous compounds. Little attention has been paid to the expression of the system in the islets of Langerhans. The current study has examined the expression and potential role of the CYP1A family within the islets of Langerhans of control and 3-methylcholanthrene (3-MC)-induced Wistar rats. 2 CYP1A expression within pancreatic slices and islets from 3-MC-induced and control rats demonstrated that CYP1A-like protein levels were induced by 3-MC pretreatment (25 mg kg 71 day 71 ; i.p. for 3 days). 3 E ects of 3-MC-induction on b-cell secretory responsiveness were investigated by use of rat collagenase-isolated islets. Insulin release from control islets incubated with 3 mM glucose (basal) was 1.4+0.2 ng/islet h 71 (mean+s.e.mean, n=7). Incubation with 16.7 mM glucose, 25 mM KCl, 100 mM arachidonic acid, or 100 mM carbachol caused a 4.4, 7.0, 4.0 and 4.2 fold, respectively, increase in insulin release (P50.001). Forskolin (2 mM), or phorbol 12-myristic 13-acetate (10 nM) potentiated glucosestimulated insulin release 1.2 and 1.6 fold (P50.01) whereas adenalin (1 mM) caused a 76% inhibition (P50.01). 4 Islets from 3-MC pretreated animals displayed similar responsiveness to all agents tested except arachidonic acid, carbachol and forskolin. Insulin release in response to arachidonic acid and carbachol was enhanced 5.2 and 5.0 fold, respectively, by 3-MC pretreatment (P50.001 compared to control islets incubated with 3 mM glucose); the e ect of forskolin on insulin output was signi®cantly decreased (20%; P50.01) compared to control islets. 5 3-MC pretreatment did not cause any signi®cant di erences in food intake, plasma glucose or total islet insulin content. Incubation of islets with 3-MC in vitro (1 mM ± 10 mM) did not a ect basal or glucose-stimulated insulin release. 6 These data suggest that CYP1A-like protein expression within the pancreatic islets of Langerhans is inducible and may have a role in the alteration of pancreatic b-cell secretory responsiveness.

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Arachidonic acid-induced insulin secretion from rat islets of Langerhans is not mediated by protein phosphorylation

Cited by 14 publications

References 30 publications

Stimulation of Islet Protein Kinase C Translocation by Palmitate Requires Metabolism of the Fatty Acid

Stimulation of Islet Protein Kinase C Translocation by Palmitate Requires Metabolism of the Fatty Acid

Mechanisms of the Stimulation of Insulin Release by Saturated Fatty Acids: A Study of Palmitate Effects in Mouse β-cells

Cytochrome P450 1A‐like proteins expressed in the islets of Langerhans and altered pancreatic β‐cell secretory responsiveness

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