Dysfunctional glycogen storage in a mouse model of α 1- antitrypsin deficiency Academic Article uri icon


MeSH Major

  • Autophagy
  • Glycogen
  • Glycogen Storage Disease
  • Liver
  • Liver Diseases
  • alpha 1-Antitrypsin


  • Autophagy is an intracellular pathway that contributes to the degradation and recycling of unfolded proteins. Based on the knowledge that autophagy affects glycogen metabolism and that alpha(1)-antitrypsin (AAT) deficiency is associated with an autophagic response in the liver, we hypothesized that the conformational abnormalities of the Z-AAT protein interfere with hepatocyte glycogen storage and/or metabolism. Compared with wild-type mice (WT), the Z-AAT mice had lower liver glycogen stores (P < 0.001) and abnormal activities of glycogen-related enzymes, including acid alpha-glucosidase (P < 0.05) and the total glycogen synthase (P < 0.05). As metabolic consequences, PiZ mice demonstrated lower blood glucose levels (P < 0.05), lower body weights (P < 0.001), and lower fat pad weights (P < 0.001) compared with WT. After the stress of fasting or partial hepatectomy, PiZ mice had further reduced liver glycogen and lower blood glucose levels (both P < 0.05 compared WT). Finally, PiZ mice exhibited decreased survival after partial hepatectomy (P < 0.01 compared with WT), but this was normalized with postoperative dextrose supplementation. In conclusion, these observations are consistent with the general concept that abnormal protein conformation and degradation affects other cellular functions, suggesting that diseases in the liver might benefit from metabolic compensation if glycogen metabolism is affected.

publication date

  • February 2009



  • Academic Article



  • eng

PubMed Central ID

  • PMC2633144

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2008-0029OC

PubMed ID

  • 18688041

Additional Document Info

start page

  • 239

end page

  • 47


  • 40


  • 2