Dysfunctional glycogen storage in a mouse model of α 1- antitrypsin deficiency

Ralf H. Hubner, Philip L. Leopold, Maija Ht Kiuru, P. De Bishnu, Anja Krause, Ronald G. Crystal

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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 α 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 glyco- gen 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 a- 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.

Original languageEnglish (US)
Pages (from-to)239-247
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number2
StatePublished - Feb 1 2009
Externally publishedYes


  • Autophagy
  • Fasting
  • Glycogen degradation
  • Partial hepatectomy

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry


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