Hepatic insulin resistance and altered gluconeogenic pathway in premature baboons

Lisa McGill-Vargas, Amalia Gastaldelli, Hanyu Liang, Diana Anzueto Guerra, Teresa Johnson-Pais, Steven Seidner, Donald McCurnin, Giovanna Muscogiuri, Ralph DeFronzo, Nicolas Musi, Cynthia Blanco

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor-b, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-a from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity.

Original languageEnglish (US)
Pages (from-to)1140-1151
Number of pages12
Issue number5
StatePublished - May 1 2017

ASJC Scopus subject areas

  • Endocrinology


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