Biphasic effects of prostaglandin E2 on the human fat cell adenylate cyclase.

Kather, H; Simon, Bernd

doi:10.1172/jci109500

Cited by 52 publications

(10 citation statements)

References 10 publications

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“…Although not examined in our studies, the observations of others suggest that PGE 2 exerts its antilipolytic effect by inhibiting adenylate cyclase activation. 7 The results of our experiments and those of others we have cited are consistent with the proposal that PGE 2 is an endogenously synthesized local counterregulator of hormone-induced lipolysis. 21 Such a concept might involve the stimulation of hormone-sensitive lipase and the subsequent release of free fatty acids from triglyceride stored in adipocytes and the concurrent stimulation of cyclooxygenase, which triggers the arachidonic acid cascade that might generate PGE 2 as a counterregulator of lipolysis.…”

Section: Discussionsupporting

confidence: 92%

Characterization of Prostaglandin E2 Binding to Isolated Human Adipocytes

1985

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Prostaglandin (PG) E2 binding to fat cells and its consequent antilipolytic effect have been studied in experiments using laboratory animals, but no binding studies have yet been reported using adipocytes from humans. Consequently, we have characterized PGE2 binding to human isolated fat cells to compare the apparent binding constant to the IC50 for the antilipolytic effect of PGE2. Our data indicate that human fat cells contain binding sites that specifically recognize prostaglandins of the E series and demonstrate stereospecific recognition of the more potent of two 15-methyl-PGE2 analogues. There was no evidence for rapid metabolism of PGE2 by isolated adipocytes such as occurs in lung and liver tissue. A double-reciprocal plot of binding data obtained at saturation using [3H]PGE2 and increasing concentrations of PGE2 indicated a single class of binding sites with an apparent binding constant (0.54 nM) that agreed well with the IC50 (0.26 nM) for the antilipolytic effect of PGE2 we observed in human fat cells. The findings from these binding and lipolysis studies are in general agreement with published observations using adipocytes from rodents and provide evidence that the conclusions reached from previous studies of laboratory animals are relevant to adipocyte physiology in humans.

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Section: Discussionsupporting

confidence: 92%

Characterization of Prostaglandin E2 Binding to Isolated Human Adipocytes

1985

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“…Because PGE 2 is usually found to stimulate adenylate cylcase activity in other cell types, it may seem unusual to suggest that it is an inhibitor of this enzyme in HIT cells and possibly in normal islet (3-cells. However, precedent exists for inhibitory effects of PGE 2 on adenylate cyclase activity in isolated adipocytes (20) and renal cortical cells (21).…”

Section: Discussionmentioning

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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“…These results suggest that age or, alternatively, metabolic changes which occur during the aging process, is an important factor in the action of nicotinic acid in adipose tissue. Its antilipolytic effect is known to be mediated by cyclic AMP (Andersson, Harthon, Hedstrom & Lundholm, 1973;Kather & Simon, 1979). As rats grow older, hormone-induced adenylate cyclase activity in adipose tissue decreases, with a simultaneous increase of phosphodiesterase activity (Forn et al, 1970;Giudicelli & Pecquery, 1978).…”

Section: Discussionmentioning

confidence: 99%

Age related changes in the antilipolytic effects of nicotinic acid in rat adipose tissue

Caparrotta

Fassina

Gaion

et al. 1983

British J Pharmacology

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1The effect of nicotinic acid on lipolysis was tested in vitro in adipose tissue from three groups of rats, selected according to age: 6-7 weeks, 10-12 weeks and 16-20 weeks old. 2 Although the changes were not statistically significant, the basal release of free fatty acid (FFA) was increased and glycerol was decreased by nicotinic acid (0.01-1 mM); the drug caused a statistically significant increase in basal FFA: glycerol ratio in a concentration-dependent manner. This ratio also increased with age in the absence of drug.3 (-)-Noradrenaline (10 IM) and theophylline (3mM) each stimulated lipolysis. When glycerol release was calculated as a percentage increase, the effects of these drugs became more marked with age. By contrast, the highest absolute rate of induced release occurred in adipose tissue from the youngest rats.4 The lipolytic effect of 10 t4M (-)-noradrenaline was generally unaffected by nicotinic acid except in adipose tissue from the oldest rats when the glycerol release was reduced by 1 mM nicotinic acid, although it did not alter FFA: glycerol ratio. 5 The stimulation of glycerol release induced by 3 mM theophylline was not affected by the presence of nicotinic acid in the youngest rats, but the drug elicited a concentration-dependent antilipolytic effect in adipose tissue from 10-12 weeks old rats, which was even more pronounced in the oldest animals. Lower theophylline concentrations (0.6-1 mM) were also sensitive to nicotinic acid inhibition in the 6-7 weeks old rats. In the presence of theophylline, nicotinic acid had no effect on FFA: glycerol ratio. 6 These data show a direct influence of age on the antilipolytic action of nicotinic acid.

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Biphasic effects of prostaglandin E2 on the human fat cell adenylate cyclase.

Cited by 52 publications

References 10 publications

Characterization of Prostaglandin E2 Binding to Isolated Human Adipocytes

Characterization of Prostaglandin E2 Binding to Isolated Human Adipocytes

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

Age related changes in the antilipolytic effects of nicotinic acid in rat adipose tissue

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