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Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons
- Source :
- Endocrinology. 158:1140-1151
- Publication Year :
- 2017
- Publisher :
- The Endocrine Society, 2017.
-
Abstract
- 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–β, 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-α 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.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Term Birth
medicine.medical_treatment
03 medical and health sciences
0302 clinical medicine
Endocrinology
Insulin resistance
Pregnancy
030225 pediatrics
Internal medicine
Diabetes mellitus
medicine
Animals
Insulin
Glycogen synthase
Fetus
biology
Animal
business.industry
Gluconeogenesis
Metabolic Networks and Pathway
medicine.disease
Insulin receptor
Glucose
030104 developmental biology
Animals, Newborn
Liver
Hyperglycemia
biology.protein
Premature Birth
Female
Blood sugar regulation
Insulin Resistance
Metabolic syndrome
business
Special Section: Metabolism in Endocrine Health and Disease
Gluconeogenesi
Metabolic Networks and Pathways
Papio
Subjects
Details
- ISSN :
- 19457170 and 00137227
- Volume :
- 158
- Database :
- OpenAIRE
- Journal :
- Endocrinology
- Accession number :
- edsair.doi.dedup.....6b3950398b23b07c51dc581b5db842d8