TY - JOUR
T1 - Effect of adrenal medullectomy on metabolic responses to chronic intermittent hypoxia in the frequently sampled intravenous glucose tolerance test
AU - Shin, Mi Kyung
AU - Han, Woobum
AU - Joo, Hoon
AU - Bevans-Fonti, Shannon
AU - Shiota, Masakazu
AU - Stefanovski, Darko
AU - Polotsky, Vsevolod Y.
N1 - Funding Information:
This work was supported by the National Heart, Lung, and Blood Institute Grants R01-HL-080105, R01-HL-128970 and R01-HL-133100, and the American Sleep Medicine Foundation Grant 133-BS-15 (to V. Y. Polotsky) and by the American Heart Association Grant 12POST11820001 (to M.-K. Shin).
Publisher Copyright:
Copyright © 2017 the American Physiological Society.
PY - 2017
Y1 - 2017
N2 - 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 SG but did not affect SI and AIRG. Adrenal 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.
AB - 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 SG but did not affect SI and AIRG. Adrenal 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.
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U2 - 10.1152/japplphysiol.00975.2016
DO - 10.1152/japplphysiol.00975.2016
M3 - Article
C2 - 28104753
AN - SCOPUS:85016942691
VL - 122
SP - 767
EP - 774
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
SN - 0161-7567
IS - 4
ER -