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Because the liver is the major organ that produces and supplies blood glucose, we aimed at defining the potential role of liver glycogen autophagy in the programming of glucose metabolism disturbances. To this end, newborns were obtained from pregnant Wistar rats fed ad libitum with a standard diet or 65% food-restricted during the last week of gestation. We found that newborns from undernourished mothers showed markedly high basal insulin levels whereas those of glucagon were decreased. This unbalance led to activation of the mTORC1 pathway and inhibition of hepatic autophagy compromising the adequate handling of glycogen in the very early hours of extrauterine life. Restoration of autophagy with rapamycin but not with glucagon, indicated no defect in autophagy machinery per se<jats:italic>,<\/jats:italic> but in signals triggered by glucagon. Taken together, these results support the notion that hyperinsulinemia is an important mechanism by which mobilization of liver glycogen by autophagy is defective in food-restricted animals. This early alteration in the hormonal control of liver glycogen autophagy may influence the risk of developing metabolic diseases later in life.<\/jats:p>","DOI":"10.1038\/s41598-020-74702-9","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T10:09:45Z","timestamp":1603102185000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats"],"prefix":"10.1038","volume":"10","author":[{"given":"Juan","family":"de Toro-Mart\u00edn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Fern\u00e1ndez-Marcelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1gueda","family":"Gonz\u00e1lez-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Escriv\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela M.","family":"Valverde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"\u00c1lvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Fern\u00e1ndez-Mill\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,19]]},"reference":[{"key":"74702_CR1","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1152\/physrev.1992.72.2.507","volume":"72","author":"J Girard","year":"1992","unstructured":"Girard, J., Ferr\u00e9, P., P\u00e9gorier, J. 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