title: Impaired glucose homeostasis after a transient intermittent hypoxic exposure in neonatal rats.
abstract: This initial report presents a neonatal rat model with exposure to a transient intermittent hypoxia (IH), which results in a persisting diabetes-like condition in the young rats. Twenty-five male pups were treated at postnatal day 1 with IH exposure by alternating the level of oxygen between 10.3% and 20.8% for 5h. The treated animals were then maintained in normal ambient oxygen condition for 3 week and compared to age-matched controls. The IH treated animals exhibited a significantly higher fasting glucose level than the control animals (237.00 ± 19.66 mg/dL vs. 167.25 ± 2.95 mg/dL; P=0.003); and a significantly lower insulin level than the control (807.0 ± 72.5 pg/mL vs. 1839.8 ± 377.6 pg/mL; P=0.023). There was no difference in the mass or the number of insulin producing beta cells as well as no indicative of inflammatory changes; however, glucose tolerance tests showed a significantly disturbed glucose homeostasis. In addition, the amount of C-peptide secreted from the islets harvested from the IH animals were decreased significantly (from 914 pM in control to 809 pM in IH; P=0.0006) as well. These observations demonstrate that the neonatal exposure to the IH regimen initiates the development of deregulation in glucose homeostasis without infiltration of inflammatory cells.
authors.affiliation: UCLA, School of Dentistry, LA, CA 90095, United States. Electronic address: epae@umaryland.edu.
authors.forename: Eung-Kwon
authors.initials: EK
authors.lastname: Pae
authors.forename: Bhoomika
authors.initials: B
authors.lastname: Ahuja
authors.forename: Marieyerie
authors.initials: M
authors.lastname: Kim
authors.forename: Gyuyoup
authors.initials: G
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000378:metabolism; D002452:Cell Count; D015687:Cell Hypoxia; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology; D005215:Fasting; D006706:Homeostasis; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D010100:Oxygen
keywords: Diabetes; GAD65; IH; IL; Intermittent hypoxia; Neonatal model; Pancreatic beta cells; glutamate decarboxylase65; interleukin; intermittent hypoxia