Salicylate Intoxication and Glucose-Induced Insulin Secretion in the Rat

García, J A Vázquez; Arata, M; Me, Fernández; Astolfi, E; Jc, Basabe

doi:10.1055/s-2007-1019076

Cited by 5 publications

(4 citation statements)

References 3 publications

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“…Since in normal man treatment with other inhibitors of PG synthesis, such as ibuprofen [5] or indomethacin [7,8], is associated with unaltered or decreased insulin responsiveness to glucose, respectively, it may be assumed that the different effects of these drugs may be due to actions apart from inhibiting PG synthesis. As to experiments in vitro, sodium salicylate has been shown to augment glucose-induced insulin release by the isolated perfused rat pancreas [22], and by monolayer cultures of rat pancreatic cells [23], but not by hamster islets [24].…”

Section: Discussionmentioning

confidence: 99%

“…An effect on plasma insulin is not seen, when indomethacin or ibuprofen [5] is employed instead of ASA. Although a great deal of in-vitro data directly demonstrate that ASA along with other inhibitors of PG synthesis stimulate insulin secretion [22,23], species differences may exist [24] and invitro experiments may not accurately reflect hormonal events in intact man. Several studies have demonstrated that salicylate or ASA lower plasma glucose in normal subjects [191 and Type 2 diabetic patients [3,4].…”

Section: Discussionmentioning

confidence: 99%

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Acetyl-salicylic acid impairs insulin-mediated glucose utilization and reduces insulin clearance in healthy and non-insulin-dependent diabetic man

et al. 1985

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The effect of acetyl-salicylic acid (ASA, 3 g per day for 3 days) on glucose utilization and insulin secretion was studied in healthy volunteers and Type 2 diabetic patients using the hyperglycaemic and euglycaemic insulin clamp technique. When in healthy subjects arterial plasma glucose was acutely raised and maintained at +7 mmol/l above fasting level, the plasma insulin response was enhanced by ASA (70 +/- 7 vs. 52 +/- 7 mU/l), whereas the plasma C-peptide response was identical. Despite higher insulin concentrations, glucose utilization was not significantly altered (control, 61 +/- 7; ASA, 65 +/- 6 mumol X kg-1 X min-1) indicating impairment of tissue sensitivity to insulin by ASA. Inhibition of prostaglandin synthesis was not likely to be involved in the effect of ASA, since insulin response and glucose utilization were unchanged following treatment with indomethacin. In the euglycaemic insulin (1 mU X kg-1 X min-1) clamp studies, glucose utilization was unaltered by ASA despite higher insulin concentrations achieved during constant insulin infusion (103 +/- 4 vs. 89 +/- 4 mU/l). In Type 2 diabetic patients, fasting hyperglycaemia (10.6 +/- 1.1 mmol/l) and hepatic glucose production (15 +/- 2 mumol X kg-1 X min-1) fell upon ASA treatment (8.6 +/- 0.7 mmol/l; 13 +/- 1 mumol X kg-1 X min-1). During the hyperglycaemic clamp study, the plasma response of insulin, but not of C-peptide, was enhanced by ASA, whereas tissue sensitivity to insulin was reduced by 30 percent.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acetyl-salicylic acid impairs insulin-mediated glucose utilization and reduces insulin clearance in healthy and non-insulin-dependent diabetic man

et al. 1985

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“…Diabetes 36:1047-53,1987 P rostaglandin E 2 (PGE 2 ) inhibits glucose-induced insulin secretion in humans, animals, and some in vitro pancreatic islet preparations (1)(2)(3)(4)(5)(6). Inhibitors of PGE 2 synthesis augment glucose-induced insulin secretion both in vivo (1,2,7,8) and in vitro (9)(10)(11)(12) and partially restore defective insulin secretion in type II diabetic patients (1,8,13). Despite the reproducible nature of these findings, confusion exists regarding prostaglandin regulation of insulin secretion.…”

Section: Sulfate-polyacrylamide Gels Revealed Adp-ribosylation Of a Cmentioning

confidence: 95%

Receptor-Mediated Adenylate Cyclase—Coupled Mechanism for PGE2 Inhibition of Insulin Secretion in HIT Cells

et al. 1987

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Prostaglandin E2 (PGE2) inhibits glucose-induced insulin secretion, and inhibitors of PGE2 synthesis augment this event. However, there has been confusion regarding prostaglandin regulation of insulin secretion, partly because no mechanism has been demonstrated for the inhibitory action of PGE2 on beta-cell function. These studies were performed with a clonal cell line of glucose-responsive beta-cells (HIT cells) to determine whether PGE2 effects on insulin secretion are receptor mediated and, if so, whether the postreceptor effects are mediated by inhibitory regulatory components (Ni) of adenylate cyclase. Saturable [3H]PGE2 binding to HIT cells was demonstrated. This binding was dissociable and specific for prostaglandins of the E series. Scatchard analyses of binding data indicated a single class of sites with a Kd of approximately 1 X 10(-9) M. Guinea pig islets were also demonstrated to have a single class of binding sites with a similar Kd but only 22% as many binding sites (0.060 vs. 0.013 pmol/mg protein, HIT cells vs. guinea pig islet). HIT cells were demonstrated to synthesize PGE2, and this synthesis was inhibitable by acetylsalicylic acid. Accumulation of cAMP by HIT cells was inhibited in a concentration-dependent manner by PGE2 with an IC50 of approximately 1 X 10(-9) M. Insulin secretion by HIT cells during static incubations with 11.1 mM glucose was also inhibited by PGE2 in a concentration-dependent manner with an IC50 of 1 X 10(-9) M. PGE2 was more potent than epinephrine but less potent than somatostatin in this regard. Maximum inhibition of glucose-induced insulin secretion was 26, 37, and 29% of control values for somatostatin, PGE2, and epinephrine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Experiments with cyclooxygenase inhibitors also yielded disparate results, suggesting inhibition, stimulation or lack of an effect by endogenous PGs on insulin release (7,(10)(11)(12)(13).…”

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confidence: 99%

Effects of lipoxygenase and cyclooxygenase inhibitors on glucose-stimulated insulin secretion from the isolated perfused rat pancreas

Ealsh

Pek

1984

Life Sciences

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Some of the metabolites of arachidonic acid formed in the lipoxygenase and cyclooxygenase pathways stimulate insulin release. We studied the relative importance of each of these pathways in the modulation of glucose-induced insulin release by using inhibitors of arachidonate metabolism. Perfusion of the isolated rat pancreas with two chemically different inhibitors of cyclooxygenase, flurbiprofen and sodium salicylate, markedly inhibited prostaglandin E2 release, but had little effect on glucose-induced insulin release or on potentiation of insulin release caused by prior exposure to glucose. On the other hand, nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, not only inhibited both phases of glucose-induced insulin release but also abolished the potentiation effect. These effects of NDGA prevailed, when it was administered together with flurbiprofen, which caused profound inhibition of prostaglandin E2 release. We conclude that 1) lipoxygenase pathways play a dominant role in glucose-stimulated insulin release, and 2) endogenous lipoxygenase metabolites influence the potentiating effect of glucose on the release of insulin in response to a subsequent stimulation.

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Salicylate Intoxication and Glucose-Induced Insulin Secretion in the Rat

Cited by 5 publications

References 3 publications

Acetyl-salicylic acid impairs insulin-mediated glucose utilization and reduces insulin clearance in healthy and non-insulin-dependent diabetic man

Acetyl-salicylic acid impairs insulin-mediated glucose utilization and reduces insulin clearance in healthy and non-insulin-dependent diabetic man

Receptor-Mediated Adenylate Cyclase—Coupled Mechanism for PGE2 Inhibition of Insulin Secretion in HIT Cells

Effects of lipoxygenase and cyclooxygenase inhibitors on glucose-stimulated insulin secretion from the isolated perfused rat pancreas

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