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 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 to 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 -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 to WT. Following 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 following partial hepatectomy (p<0.01 compared to WT), but was normalized with post-operative 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.