title: Effects of ATP infusion on glucose turnover and gluconeogenesis in patients with advanced non-small-cell lung cancer.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Agteresch
authors.forename: S
authors.initials: S
authors.lastname: Leij-Halfwerk
authors.forename: J W
authors.initials: JW
authors.lastname: Van Den Berg
authors.forename: C H
authors.initials: CH
authors.lastname: Hordijk-Luijk
authors.forename: J H
authors.initials: JH
authors.lastname: Wilson
authors.forename: P C
authors.initials: PC
authors.lastname: Dagnelie
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000368:Aged; D000409:Alanine / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: D000255:Adenosine Triphosphate; D005947:Glucose; D000409:Alanine