{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:26:01Z","timestamp":1791285961627,"version":"4.1.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1034,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>Glycogen storage disease type Ia (GSD-Ia), which is characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA), is caused by deficiencies in the endoplasmic reticulum (ER)-associated glucose-6-phosphatase-\u03b1 (G6Pase-\u03b1 or G6PC) that hydrolyzes glucose-6-phosphate (G6P) to glucose. G6Pase-\u03b1 activity depends on the G6P transporter (G6PT) that translocates G6P from the cytoplasm into the ER lumen. The functional coupling of G6Pase-\u03b1 and G6PT maintains interprandial glucose homeostasis. We have shown previously that gene therapy mediated by AAV-GPE, an adeno-associated virus (AAV) vector expressing G6Pase-\u03b1 directed by the human<\/jats:bold>\n                      <jats:bold>G6PC<\/jats:bold>\n                      <jats:bold>promoter\/enhancer (GPE), completely normalizes hepatic G6Pase-\u03b1 deficiency in GSD-Ia (G6pc\u2212\/\u2212) mice for at least 24 weeks. However, a recent study showed that within 78 weeks of gene deletion, all mice lacking G6Pase-\u03b1 in the liver develop HCA. We now show that gene therapy mediated by AAV-GPE maintains efficacy for at least 70-90 weeks for mice expressing more than 3% of wild-type hepatic G6Pase-\u03b1 activity. The treated mice displayed normal hepatic fat storage, had normal blood metabolite and glucose tolerance profiles, had reduced fasting blood insulin levels, maintained normoglycemia over a 24-hour fast, and had no evidence of hepatic abnormalities. After a 24-hour fast, hepatic G6PT messenger RNA levels in G6pc\u2212\/\u2212 mice receiving gene therapy were markedly increased. Because G6PT transport is the rate-limiting step in microsomal G6P metabolism, this may explain why the treated G6pc\u2212\/\u2212 mice could sustain prolonged fasts. The low fasting blood insulin levels and lack of hepatic steatosis may explain the absence of HCA.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion :<\/jats:title>\n                    <jats:p>\n                      <jats:bold>These results confirm that AAV-GPE\u2013mediated gene transfer corrects hepatic G6Pase-\u03b1 deficiency in murine GSD-Ia and prevents chronic HCA formation.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.25717","type":"journal-article","created":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T09:20:08Z","timestamp":1331803208000},"page":"1719-1729","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":76,"title":["Prevention of hepatocellular adenoma and correction of metabolic abnormalities in murine glycogen storage disease type Ia by gene therapy"],"prefix":"10.1097","volume":"56","author":[{"given":"Young Mok","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Sik","family":"Jun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Jiunn","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Ru","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lane H.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Mansfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice Y.","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-17-20241202","doi-asserted-by":"crossref","first-page":"676688","DOI":"10.1038\/nrendo.2010.189","article-title":"Glycogen storage disease type I and G6Pase deficiency: etiology and therapy.","volume":"6","author":"Chou","year":"2010","journal-title":"Nat Rev Endocrinol"},{"key":"R2-17-20241202","doi-asserted-by":"crossref","first-page":"423425","DOI":"10.1056\/NEJM197602192940805","article-title":"Continuous nocturnal intragastric feeding for management of type 1 glycogenstorage disease.","volume":"294","author":"Greene","year":"1976","journal-title":"N Engl J Med"},{"key":"R3-17-20241202","doi-asserted-by":"crossref","first-page":"171175","DOI":"10.1056\/NEJM198401193100306","article-title":"Cornstarch therapy in type I glycogen storage disease.","volume":"310","author":"Chen","year":"1984","journal-title":"N Engl J Med"},{"key":"R4-17-20241202","first-page":"276279","article-title":"Hepatocellular adenomas in glycogen storage disease type I and III: a series of 43 patients and review of the literature.","volume":"24","author":"Labrune","year":"1997","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"Suppl 1","key":"R5-17-20241202","first-page":"S20S34","article-title":"Glycogen storage disease type I: diagnosis, management, clinical course and outcome. 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