title: Effect of adrenal medullectomy on metabolic responses to chronic intermittent hypoxia in the frequently sampled intravenous glucose tolerance test.
abstract: Obstructive sleep apnea is associated with type 2 diabetes. We have previously developed a mouse model of intermittent hypoxia (IH) mimicking oxyhemoglobin desaturations in patients with sleep apnea and have shown that IH increases fasting glucose, hepatic glucose output, and plasma catecholamines. We hypothesize that adrenal medulla modulates glucose responses to IH and that such responses can be prevented by adrenal medullectomy. We performed adrenal medullectomy or sham surgery in lean C57BL/6J mice, which were exposed to IH or intermittent air (control) for 4 wk followed by the frequently sampled intravenous glucose tolerance test (FSIVGTT) in unanesthetized unrestrained animals. IH was administered during the 12-h light phase (9 AM to 9 PM) by decreasing inspired oxygen from 21 to 6.5% 60 cycles/h. Insulin sensitivity (SI), insulin independent glucose disposal [glucose effectiveness (SG)], and the insulin response to glucose (AIRG) were determined using the minimal model method. In contrast to our previous data obtained in restrained mice, IH did not affect fasting blood glucose and plasma insulin levels in sham-operated mice. IH significantly decreased SGbut did not affect SIand AIRGAdrenal medullectomy decreased fasting blood glucose and plasma insulin levels and increased glycogen synthesis in the liver in hypoxic mice but did not have a significant effect on the FSIVGTT metrics. We conclude that, in the absence of restraints, IH has no effect on glucose metabolism in lean mice with exception of decreased SG, whereas adrenal medullectomy decreases fasting glucose and insulin levels in the IH environment.NEW & NOTEWORTHYTo our knowledge, this is the first study examining the role of adrenal catecholamines in glucose metabolism during intermittent hypoxia (IH) in unanesthetized unrestrained C57BL/6J mice. We report that IH did not affect fasting glucose and insulin levels nor insulin sensitivity and insulin secretion during, whereas glucose effectiveness was decreased. Adrenal medullectomy decreased fasting blood glucose and insulin levels in mice exposed to IH but had no effect on glucose metabolism, insulin secretion, and insulin sensitivity.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Shin
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Woobum
authors.initials: W
authors.lastname: Han
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Hoon
authors.initials: H
authors.lastname: Joo
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Shannon
authors.initials: S
authors.lastname: Bevans-Fonti
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; and.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shiota
authors.affiliation: New Bolton Center, Department of Biostatistics, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania.
authors.forename: Darko
authors.initials: D
authors.lastname: Stefanovski
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; vpolots1@jhmi.edu.
authors.forename: Vsevolod Y
authors.initials: VY
authors.lastname: Polotsky
mesh_terms: D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005215:Fasting / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test / Q000379:methods; D006003:Glycogen / Q000378:metabolism; D000860:Hypoxia / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000378:metabolism; D010108:Oxyhemoglobins / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000097:blood / Q000378:metabolism / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010108:Oxyhemoglobins; D006003:Glycogen; D005947:Glucose; D010100:Oxygen
keywords: glucose effectiveness; insulin resistance; obstructive sleep apnea; type 2 diabetes