Effect of Salicylate Infusion on Plasma-Insulin and Glucose Tolerance in Healthy Persons and Mild Diabetics

Field, J B; Boyle, Constance; Remer, Adrienne

doi:10.1016/s0140-6736(67)92842-5

Cited by 48 publications

(15 citation statements)

References 12 publications

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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: 99%

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

confidence: 99%

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

et al. 1987

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“…S ODIUM salicylate and acetylsalicylate have been reported to enhance glucose-induced insulin secretion in vitro and in vivo (2)(3)(4)(5)(6)(7)(8)(9). Salicylates were proposed to exert their effects on pancreatic islet cells by inhibiting prostaglandin (PG) synthesis.…”

mentioning

confidence: 99%

The Effect of Flurbiprofen, a Potent Inhibitor of Prostaglandin Synthesis, on Insulin and Glucagon Release from Isolated Rat Pancreas^*

1984

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The influence of different levels of inhibition of prostaglandin (PG) synthesis on the release of insulin and glucagon was investigated in the basal state (5.6 mM glucose) and in response to 30-min perfusion of 16.7 mM glucose using the isolated perfused rat pancreas model. Flurbiprofen (FLR), a potent and selective inhibitor of PG synthesis, was present in the perfusate during the entire experimental period at a concentration of 10(-8), 5 X 10(-8), or 10(-6) M; control experiments were performed without the drug. Levels of immunoreactive PGE2, PGF2 alpha, insulin, and glucagon were measured in the portal venous effluent. FLR inhibited PG synthesis in a dose-related manner; PGE2 was inhibited more than PGF2 alpha. Basal and glucose-induced secretion of insulin was augmented by FLR at 5 X 10(-8) M, but was inhibited at 10(-6) M. At 10(-6) M FLR, basal glucagon secretion was inhibited; glucose-induced suppression still occurred without any potentiation. We conclude that 1) endogenous PGs modulate the secretion of insulin and glucagon; 2) divergence of the effects of low and high levels of inhibition of PG biosynthesis on insulin release may be due to altered tissue proportions of various PGs and related autacoids; and 3) the predominant effect of endogenous PGs on glucagon release is tonic stimulation.

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“…Similarly, elevation of plasma insulin concentration (Field et al, 1967;Guigliano etal., 1978;Chen & Robertson, 1979) has been confirmed (Figure 2). In addition sali- (Figure 4a, b).…”

Section: Discussionmentioning

confidence: 96%

Enhancement by sodium salicylate of the blood glucose lowering effect of chlorpropamide‐drug interaction or summation of similar effects?

Richardson¹,

Foster²,

Mawer³

1986

Brit J Clinical Pharma

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1 The ability of sodium salicylate (3 g) to enhance the blood glucose lowering action of chlorpropamide (200 mg) has been confirmed in healthy male volunteers who received an oral test dose of 50 g glucose. Salicylate raised the plasma concentration of insulin and lowered that of cortisol but did not alter the concentration of chlorpropamide. 2 The area under the blood glucose concentration-time curve was used as the measure of drug response and the significance of drug effects was assessed by analysis of variance. In one study on five volunteers the effect of combining salicylate and chlorpropamide was additive. In a second study on six volunteers 200 mg chlorpropamide, 3 g sodium salicylate and 100 mg chlorpropamide + 1.5 g salicylate were equi-effective. 3 The enhancement of chlorpropamide action by salicylate in this single dose study is consistent with the summation of similar effects. It is not necessary to postulate an interaction.

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Effect of Salicylate Infusion on Plasma-Insulin and Glucose Tolerance in Healthy Persons and Mild Diabetics

Cited by 48 publications

References 12 publications

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

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

The Effect of Flurbiprofen, a Potent Inhibitor of Prostaglandin Synthesis, on Insulin and Glucagon Release from Isolated Rat Pancreas^*

Enhancement by sodium salicylate of the blood glucose lowering effect of chlorpropamide‐drug interaction or summation of similar effects?

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Effect of Salicylate Infusion on Plasma-Insulin and Glucose Tolerance in Healthy Persons and Mild Diabetics

Cited by 48 publications

References 12 publications

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

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

The Effect of Flurbiprofen, a Potent Inhibitor of Prostaglandin Synthesis, on Insulin and Glucagon Release from Isolated Rat Pancreas*

Enhancement by sodium salicylate of the blood glucose lowering effect of chlorpropamide‐drug interaction or summation of similar effects?

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The Effect of Flurbiprofen, a Potent Inhibitor of Prostaglandin Synthesis, on Insulin and Glucagon Release from Isolated Rat Pancreas^*