Alcohol and Alcoholism Advance Access originally published online on May 10, 2006
Alcohol and Alcoholism 2006 41(4):372-378; doi:10.1093/alcalc/agl032
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ARGININE CHALLENGE UNRAVELS PERSISTENT DISTURBANCES OF UREA CYCLE AND GLUCONEOGENESIS IN ABSTINENT ALCOHOLICS
1 Division of Clinical Neuroscience, Max-Planck-Institute of Experimental Medicine, 2 Department of Clinical Chemistry, Georg-August-University, Göttingen, Germany and 3 Institute of Physiology and Pathophysiology, Ruprecht-Karls-University, Heidelberg, Germany
* Author to whom correspondence should be addressed at: Tel.: +49 551 3899 628; Fax: +49 551 3899 670; E-mail: ehrenreich{at}em.mpg.de
(Received 27 October 2005; first review notified 9 January 2006; in revised form 22 March 2006; accepted 23 March 2006)
Aims: Data on recovery from hormonal and metabolic sequelae of alcoholism in strictly controlled alcohol abstinence are mainly restricted to short-term abstention. Our previous findings of persistently decreased plasma and urinary urea concentrations in long-term abstinent alcoholics prompted us to further elucidate this unexplained phenomenon. Methods: The response of circulating urea cycle metabolites and glucose-regulating hormones to an intravenous load (30 g) of arginine hydrochloride was investigated in abstinent male alcoholics (n = 14) after complete recovery of all routine liver parameters and compared with that in healthy male controls (n = 15). Results: The arginine challenge provoked (i) higher peak concentrations of arginine and increased arginine/ornithine and ornithine/citrulline ratios in the plasma of abstinent alcoholics; (ii) augmented plasma glutamine concentrations in alcoholics in the presence of comparable levels in both experimental groups of plasma glutamate, ammonia, and nitrate/nitrite; (iii) parallel increases in plasma urea concentrations over the respective baseline levels but distinctly higher urinary urea excretion in controls; (iv) a blunted blood glucose response to arginine in alcoholics together with a reduced insulin and glucagon surge; and (v) an elevated growth hormone peak as compared with controls. Conclusions: Application of an intravenous arginine challenge reveals profound and lasting metabolic and hormonal disturbances in abstinent alcoholics, affecting urea cycle and gluconeogenesis. The common denominator of many of these changes may be an acquired irreversible deficiency in cellular energy regulation.