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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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
Pages (from-to)239-247
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume40
Issue number2
DOIs
Publication statusPublished - 1 Feb 2009
Externally publishedYes

Fingerprint

Glycogen
Metabolism
Liver Glycogen
Liver
Blood Glucose
Glucosidases
Degradation
Glycogen Synthase
Proteins
Autophagy
Hepatectomy
Conformations
Recycling
Fats
Glucose
Protein Unfolding
Protein Conformation
Acids
Enzymes
Proteolysis

Keywords

  • Autophagy
  • Fasting
  • Glycogen degradation
  • Partial hepatectomy

ASJC Scopus subject areas

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

Cite this

Dysfunctional glycogen storage in a mouse model of α 1- antitrypsin deficiency. / Hubner, Ralf H.; Leopold, Philip L.; Kiuru, Maija; De Bishnu, P.; Krause, Anja; Crystal, Ronald.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 40, No. 2, 01.02.2009, p. 239-247.

Research output: Contribution to journalArticle

Hubner, Ralf H. ; Leopold, Philip L. ; Kiuru, Maija ; De Bishnu, P. ; Krause, Anja ; Crystal, Ronald. / Dysfunctional glycogen storage in a mouse model of α 1- antitrypsin deficiency. In: American Journal of Respiratory Cell and Molecular Biology. 2009 ; Vol. 40, No. 2. pp. 239-247.
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