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Dysfunctional glycogen storage in a mouse model of alpha1-antitrypsin deficiency.
- Source :
-
American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2009 Feb; Vol. 40 (2), pp. 239-47. Date of Electronic Publication: 2008 Aug 07. - Publication Year :
- 2009
-
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 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.
- Subjects :
- Animals
Blood Glucose genetics
Blood Glucose metabolism
Disease Models, Animal
Glycogen genetics
Glycogen Storage Disease genetics
Glycogen Synthase genetics
Glycogen Synthase metabolism
Humans
Liver pathology
Liver Diseases genetics
Mice
Mice, Transgenic
Pulmonary Emphysema genetics
Pulmonary Emphysema metabolism
alpha-Glucosidases genetics
alpha-Glucosidases metabolism
Autophagy genetics
Glycogen metabolism
Glycogen Storage Disease metabolism
Liver metabolism
Liver Diseases metabolism
alpha 1-Antitrypsin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1535-4989
- Volume :
- 40
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of respiratory cell and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 18688041
- Full Text :
- https://doi.org/10.1165/rcmb.2008-0029OC