Stimulation of renal gluconeogenesis by exogenous adenine nucleotides

Saggerson, E D; Carpenter, Carol A.; Veiga, J. A. S.

doi:10.1016/0304-4165(83)90281-7

Cited by 13 publications

(14 citation statements)

References 14 publications

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“…When the assays performed with pig and rat brush-border membrane vesicles were compared, it resulted that the ecto-adenosine deaminase activity was higher in the vesicles from pig, suggesting that the degree of adenosine deamination in the renal tubules may vary among species. In fact, Saggerson et al (1991) reported that extracellular ATP was rapidly and mainly metabolized to adenosine and further to inosine, hypoxanthine, xanthine and uric acid by rat kidney tubule fragments, and h l i c et al (1990) found adenosine as end product in adenine nucleotide catabolism in rat renal brush-border membranes. In contrast, exogenous ATP degradation via adenosine to hypoxanthine was detected in rabbit isolated kidney tubules (Weinberg et al, 1988;Barfuss et al, 1992).…”

Section: Resultsmentioning

confidence: 99%

Adenine nucleotides and adenosine metabolism in pig kidney proximal tubule membranes

Blanco

Canela

Sayós

et al. 1993

Journal Cellular Physiology

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Exogenous adenosine triphosphate (ATP) added to brush-border membrane vesicles was rapidly degraded mainly to inosine according to the high ecto-nucleotidase activities in these vesicles. In the absence of phosphate, inosine was slowly transformed into hypoxanthine, and xanthine oxidase and dehydrogenase activities were not detected. The presence of ecto-adenosine deaminase and ecto-adenosine monophosphate (AMP) nucleotidase was shown. The ecto-adenosine deaminase was inhibited by deoxycoformycin and was also detected in rat renal brush-border membrane vesicles. Using orthovanadate, levamisole, and alpha, beta-methylene adenosine diphosphate as possible inhibitors, alkaline phosphatase was shown to be the main agent responsible for ecto-AMP nucleotidase activity. In pig renal basolateral membrane vesicles and in whole cell extracts from pig renal cortex, ecto-AMP nucleotidase was the limiting factor in ATP degradation. Comparing the ATP catabolism in the whole cell cortical extract with the catabolism in the same sample precleared of membranes, it was shown that ectonucleotidase activity is mainly bound to the membranous components. It is also shown that the whole cell extract of pig renal cortex has hypoxanthine phosphoribosyl transferase activity, and it seems probable that the rapid and specific formation of luminal inosine and its transport into the cell in competition with adenosine may start the purine salvage pathway through the synthesis of IMP from hypoxanthine.

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Section: Resultsmentioning

confidence: 99%

Adenine nucleotides and adenosine metabolism in pig kidney proximal tubule membranes

Blanco

Canela

Sayós

et al. 1993

Journal Cellular Physiology

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“…In vitro studies have shown that ATP administration stimulates gluconeogenesis from lactate [32,33], pyruvate [32,34] and glutamine [32,33,35,36]. 50 %, whereas no change was shown during low-dose ATP infusion (37-50 µg:min −" :kg −" ).…”

Section: Discussionmentioning

confidence: 99%

“…These might include receptor-stimulating and catecholamine hormone-stimulating effects of ATP. Noradrenaline is an activator of gluconeogenesis [32,47] and glycogenolysis [47]. Furthermore, ATP was shown to act as a co-transmitter of the catecholamine noradrenaline in the nervous system, and was suggested to modulate the release of other neurotransmitters [46].…”

Section: Discussionmentioning

confidence: 99%

Effects of ATP infusion on glucose turnover and gluconeogenesis in patients with advanced non-small-cell lung cancer

et al. 2000

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Cancer cachexia is associated with elevated lipolysis, proteolysis and gluconeogenesis. ATP infusion has been found to significantly inhibit loss of body weight, fat mass and fat-free mass in patients with advanced lung cancer. The present study was aimed at exploring the effects of ATP on whole-body glucose turnover, alanine turnover and gluconeogenesis from alanine. Twelve patients with advanced non-small-cell lung cancer (NSCLC) were studied 1 week before and during 22-24 h of continuous ATP infusion. After an overnight fast, turnover rates of glucose and alanine, and gluconeogenesis from alanine, were determined using primed constant infusions of ¿6, 6-(2)H(2)ğlucose and ¿3-(13)Călanine. Thirteen NSCLC patients and eleven healthy subjects were studied as control groups without ATP infusion. During high-dose ATP infusion (75 microg.min(-1).kg(-1)), glucose turnover was 0.62+/-0.07 mmol.h(-1).kg(-1), compared with 0. 44+/-0.13 mmol.h(-1).kg(-1) at baseline (P=0.04). For gluconeogenesis a similar, but non-significant, trend was observed ¿baseline, 0.30+/-0.16 mmol.h(-1).kg(-1); during ATP, 0.37+/-0.13 mmol.h(-1).kg(-1) (P=0.08). At lower ATP doses (37-50 microg. min(-1).kg(-1)) these effects were not detected. The relative increase in glucose turnover during ATP infusion compared with baseline showed a significant correlation with the ATP dose (r=0.58, P=0.02). No change in alanine turnover was observed at any ATP dose. The results of this study indicate an increase in glucose turnover during high-dose ATP infusion compared with baseline levels. During high-dose ATP infusion, glucose turnover was similar to that during low-dose ATP infusion and to that in control NSCLC patients. Between ATP infusions, however, glucose turnover in patients treated with high-dose ATP was significantly lower than that in the low-dose and control NSCLC patients (P=0.04 and P=0.03 respectively), and similar to that in healthy subjects. This would suggest that repeated high-dose ATP infusions may inhibit glucose turnover between infusion periods.

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“…Cellular uptake ofextracellular ATP has been proposed (26)(27)(28), however, recent studies in proximal convoluted tubule suspensions are not consistent with this mechanism (23,24). Exogenous ATP is rapidly degraded in tubular suspensions (22)(23)(24)29). ATP, as well as ADP and AMP, increase intracellular ATP (22,23).…”

Section: Discussionmentioning

confidence: 99%

Role of adenosine triphosphate (ATP) and NaK ATPase in the inhibition of proximal tubule transport with intracellular cystine loading.

Coor¹,

Salmon²,

Quigley³

et al. 1991

J. Clin. Invest.

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Cellular cystine loading with cystine dimethyl ester inhibits volume absorption, transepithelial potential difference, glucose transport, and bicarbonate transport in proximal convoluted tubules perfused in vitro. This study examined the roles of ATP and NaK ATPase in this in vitro model of the Fanconi syndrome of cystinosis. Intracellular ATP was measured using the luciferin-luciferase assay. Intracellular ATP was reduced by 60% in proximal convoluted tubules incubated with 0.5 mM cystine dimethyl ester for 15 min at 37°C (P < 0.001). Incubation of cystine loaded tubules with 1 mM exogenous ATP increased intracellular ATP to levels not significantly different than that of controls. On the other hand, Vmax NaK ATPase activity was unchanged even though the incubation times and the concentration of cystine dimethyl ester were doubled to 30 min and 1 mM, respectively. In proximal convoluted tubules perfused in vitro, 0.5 mM cystine dimethyl ester resulted in an 89% inhibition in volume absorption (0.81±0.14 to 0.09±0.09 nl/mm * min), while there was only a 45% inhibition in volume absorption (P < 0.01) due to cellular cystine loading in the presence of 1 mM lumen and bath ATP (0.94±0.05 to 0.52±0.11 nl/mm-min). These data demonstrate that proximal tubule cellular cystine loading decreases cellular ATP concentration, but does not directly inhibit NaK ATPase activity. The inhibition in transport and decrease in intracellular ATP due to cellular cystine loading was ameliorated by exogenous ATP. These data are consistent with cellular ATP depletion playing a major role in the inhibition of proximal tubule transport due to intracellular cystine loading. (J. Clin. Invest. 1991. 87:955-961.)

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Stimulation of renal gluconeogenesis by exogenous adenine nucleotides

Cited by 13 publications

References 14 publications

Adenine nucleotides and adenosine metabolism in pig kidney proximal tubule membranes

Adenine nucleotides and adenosine metabolism in pig kidney proximal tubule membranes

Effects of ATP infusion on glucose turnover and gluconeogenesis in patients with advanced non-small-cell lung cancer

Role of adenosine triphosphate (ATP) and NaK ATPase in the inhibition of proximal tubule transport with intracellular cystine loading.

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