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Alcohol and Alcoholism Advance Access published online on May 10, 2006
Alcohol and Alcoholism, doi:10.1093/alcalc/agl032
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© The Author 2006. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved
Received October 27, 2005
Revised March 22, 2006
Accepted March 23, 2006

Article

ARGININE CHALLENGE UNRAVELS PERSISTENT DISTURBANCES OF UREA CYCLE AND GLUCONEOGENESIS IN ABSTINENT ALCOHOLICS

MARTIN HASSELBLATT 1, HENNING KRAMPE 1, SILKE JACOBS 1, HEIKE SINDRAM 1, VICTOR W. ARMSTRONG 2, MARKUS HECKER 3, and HANNELORE EHRENREICH 1 *

1 Division of Clinical Neuroscience, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany
2 Department of Clinical Chemistry, Georg-August-University, Göttingen, Germany
3 Institute of Physiology and Pathophysiology, Ruprecht-Karls-University, Heidelberg, Germany

* To whom correspondence should be addressed.
HANNELORE EHRENREICH, E-mail: ehrenreich{at}em.mpg.de


  Abstract

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.


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