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. 1988 Aug 15;254(1):59–65. doi: 10.1042/bj2540059

Acute inhibition by ethanol of intestinal absorption of glucose and hepatic glycogen synthesis on glucose refeeding after starvation in the rat.

E B Cook 1, J A Preece 1, S D Tobin 1, M C Sugden 1, D J Cox 1, T N Palmer 1
PMCID: PMC1135039  PMID: 3178758

Abstract

1. Intragastric administration of ethanol (75 mmol/kg body wt.) at 1 h before glucose refeeding of 24 h-starved rats inhibited hepatic glycogen deposition (by 69%) and synthesis (by approx. 70%), but was without significant effect on muscle glycogen deposition and synthesis. 2. Treatment of ethanol-administered rats with methylpyrazole (an inhibitor of alcohol dehydrogenase) did not significantly diminish the inhibitory effect of ethanol on hepatic glycogen deposition after glucose refeeding, suggesting that the inhibition was not dependent on ethanol metabolism. 3. Ethanol delayed and diminished intestinal glucose absorption, at least in part by delaying gastric emptying. 4. At a lower dose (10 mmol/kg body wt.), ethanol inhibited hepatic glycogen repletion and synthesis without compromising intestinal glucose absorption. Ethanol inhibited glycogen deposition (by 40%) in hepatocytes from starved rats provided with glucose + lactate + pyruvate as substrates, consistent with it having a direct effect to diminish hepatic glycogen synthesis by inhibition of gluconeogenic flux at a site(s) between phosphoenolpyruvate and triose phosphate in the pathway. 5. It is concluded that ethanol acutely impairs hepatic glycogen repletion by inhibition at at least two distinct sites, namely (a) intestinal glucose absorption and (b) hepatic gluconeogenic flux.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bivens C. H., Feldman J. M. Effect of ethanol and its metabolites on insulin secretion. Q J Stud Alcohol. 1974 Jun;35(2):635–648. [PubMed] [Google Scholar]
  2. Boyd M. E., Albright E. B., Foster D. W., McGarry J. D. In vitro reversal of the fasting state of liver metabolism in the rat. Reevaluation of the roles of insulin and glucose. J Clin Invest. 1981 Jul;68(1):142–152. doi: 10.1172/JCI110230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen K. S., Lardy H. A. Multiple requirements for glycogen synthesis by hepatocytes isolated from fasted rats. J Biol Chem. 1985 Nov 25;260(27):14683–14688. [PubMed] [Google Scholar]
  4. Dinda P. K., Beck I. T., Beck M., McElligott T. F. Effect of ethanol on sodium-dependent glucose transport in the small intestine of the hamster. Gastroenterology. 1975 Jun;68(6):1517–1526. [PubMed] [Google Scholar]
  5. Ellis F. W. Effect of ethanol on plasma corticosterone levels. J Pharmacol Exp Ther. 1966 Jul;153(1):121–127. [PubMed] [Google Scholar]
  6. Foster D. W. Banting lecture 1984. From glycogen to ketones--and back. Diabetes. 1984 Dec;33(12):1188–1199. doi: 10.2337/diab.33.12.1188. [DOI] [PubMed] [Google Scholar]
  7. Gazzard B. G., Clark M. L. Alcohol and the alimentary system. Clin Endocrinol Metab. 1978 Jul;7(2):429–445. doi: 10.1016/s0300-595x(78)80027-9. [DOI] [PubMed] [Google Scholar]
  8. Hawkins R. D., Kalant H. The metabolism of ethanol and its metabolic effects. Pharmacol Rev. 1972 Mar;24(1):67–157. [PubMed] [Google Scholar]
  9. Holness M. J., French T. J., Sugden M. C. Hepatic glycogen synthesis on carbohydrate re-feeding after starvation. A regulatory role for pyruvate dehydrogenase in liver and extrahepatic tissues. Biochem J. 1986 Apr 15;235(2):441–445. doi: 10.1042/bj2350441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Katz J., Golden S., Wals P. A. Stimulation of hepatic glycogen synthesis by amino acids. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3433–3437. doi: 10.1073/pnas.73.10.3433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Katz J., McGarry J. D. The glucose paradox. Is glucose a substrate for liver metabolism? J Clin Invest. 1984 Dec;74(6):1901–1909. doi: 10.1172/JCI111610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Katz J., Wals P. A., Rognstad R. Glucose phosphorylation, glucose-6-phosphatase, and recycling in rat hepatocytes. J Biol Chem. 1978 Jul 10;253(13):4530–4536. [PubMed] [Google Scholar]
  13. Kuwajima M., Golden S., Katz J., Unger R. H., Foster D. W., McGarry J. D. Active hepatic glycogen synthesis from gluconeogenic precursors despite high tissue levels of fructose 2,6-bisphosphate. J Biol Chem. 1986 Feb 25;261(6):2632–2637. [PubMed] [Google Scholar]
  14. Lieber C. S. Metabolism and metabolic effects of alcohol. Med Clin North Am. 1984 Jan;68(1):3–31. doi: 10.1016/s0025-7125(16)31238-x. [DOI] [PubMed] [Google Scholar]
  15. Lochner A., Wulff J., Madison L. L. Ethanol-induced hypoglycemia. I. The acute effects of glucose output and peripheral glucose utilization in fasted dogs. Metabolism. 1967 Jan;16(1):1–18. doi: 10.1016/0026-0495(67)90154-0. [DOI] [PubMed] [Google Scholar]
  16. Nelson P., Wagle S. R., Ashmore J. Ethanol effects on hepatic oxidations and gluconeogenesis. Proc Soc Exp Biol Med. 1969 Jul;131(3):707–710. doi: 10.3181/00379727-131-33957. [DOI] [PubMed] [Google Scholar]
  17. Newgard C. B., Foster D. W., McGarry J. D. Evidence for suppression of hepatic glucose-6-phosphatase with carbohydrate feeding. Diabetes. 1984 Feb;33(2):192–195. doi: 10.2337/diab.33.2.192. [DOI] [PubMed] [Google Scholar]
  18. Newgard C. B., Hirsch L. J., Foster D. W., McGarry J. D. Studies on the mechanism by which exogenous glucose is converted into liver glycogen in the rat. A direct or an indirect pathway? J Biol Chem. 1983 Jul 10;258(13):8046–8052. [PubMed] [Google Scholar]
  19. Newgard C. B., Moore S. V., Foster D. W., McGarry J. D. Efficient hepatic glycogen synthesis in refeeding rats requires continued carbon flow through the gluconeogenic pathway. J Biol Chem. 1984 Jun 10;259(11):6958–6963. [PubMed] [Google Scholar]
  20. Niewoehner C. B., Gilboe D. P., Nuttall F. Q. Metabolic effects of oral glucose in the liver of fasted rats. Am J Physiol. 1984 Jan;246(1 Pt 1):E89–E94. doi: 10.1152/ajpendo.1984.246.1.E89. [DOI] [PubMed] [Google Scholar]
  21. Plapp B. V. Rate-limiting steps in ethanol metabolism and approaches to changing these rates biochemically. Adv Exp Med Biol. 1975;56:77–109. doi: 10.1007/978-1-4684-7529-6_4. [DOI] [PubMed] [Google Scholar]
  22. Postle A. D., Bloxham D. P. The use of tritiated water to measure absolute rates of hepatic glycogen synthesis. Biochem J. 1980 Oct 15;192(1):65–73. doi: 10.1042/bj1920065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Radziuk J. Sources of carbon in hepatic glycogen synthesis during absorption of an oral glucose load in humans. Fed Proc. 1982 Jan;41(1):110–116. [PubMed] [Google Scholar]
  24. Singh S. P., Patel D. G. Effects of ethanol on carbohydrate metabolism: I. Influence on oral glucose tolerance test. Metabolism. 1976 Feb;25(2):239–243. doi: 10.1016/0026-0495(76)90055-x. [DOI] [PubMed] [Google Scholar]
  25. Sugden M. C., Watts D. I., Palmer T. N., Myles D. D. Direction of carbon flux in starvation and after refeeding: in vitro and in vivo effects of 3-mercaptopicolinate. Biochem Int. 1983 Sep;7(3):329–337. [PubMed] [Google Scholar]
  26. Thomson A. D., Majumdar S. K. The influence of ethanol on intestinal absorption and utilization of nutrients. Clin Gastroenterol. 1981 May;10(2):263–293. [PubMed] [Google Scholar]
  27. Williams H. E. Alcoholic hypoglycemia and ketoacidosis. Med Clin North Am. 1984 Jan;68(1):33–38. doi: 10.1016/s0025-7125(16)31239-1. [DOI] [PubMed] [Google Scholar]
  28. Winston G. W., Reitz R. C. Effects of chronic ethanol ingestion on glucose homeostasis in males and females. Life Sci. 1980 Jan 21;26(3):201–209. doi: 10.1016/0024-3205(80)90294-5. [DOI] [PubMed] [Google Scholar]

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