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Intermittent hypoxia (IH) causes greater insulin resistance than chronic hypoxia (CH) in lean mice
Author(s) -
O'Donnell Christopher Paul,
Strollo Hilary C,
Romano Lia C,
Skalka Kristy,
Rosa Taylor C,
Stefanovski Darko,
Bergman Richard N,
GarciaOcana Adolfo,
Alonso Laura C
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.993.5
Subject(s) - intermittent hypoxia , medicine , insulin resistance , endocrinology , insulin , hypoxia (environmental) , bolus (digestion) , obstructive sleep apnea , chemistry , oxygen , organic chemistry
Sleep apnea is characterized by IH and is associated with metabolic dysfunction. We developed the first frequently sampled intravenous glucose tolerance test (FSIVGTT) in conscious mice to examine the effects of IH and CH on glucose disposal. METHODS Adult male C57BL/6J mice with chronic femoral artery and venous catheters were exposed to seven hours of either IH (nadir inspired oxygen 5‐6% at 60 cycles hr −1 ) or CH (constant 10% FIO2). Control groups were exposed to either intermittent air (IA) or were unhandled (UH). A FSIVGTT was performed by rapidly sampling arterial blood for glucose (and insulin) at (‐10), (0), (1), (2), 3, (4), 5, 6, (8), 10, (12), 14, (16), 18, (20), 25, (30), 40, 50, (60), (90), and (120) min after a bolus injection of i.v. glucose (1 g/kg). Data analysis was performed in collaboration with the Bergman group at USC utilizing the previously validated Minimal Model program. RESULTS Compared with the UH and IA groups, the IH group demonstrated a decrease in glucose effectiveness (Sg), and marked decreases in insulin sensitivity (SI) and the Disposition Index (DI) for glucose. The CH group also showed a decrease in Sg, but SI and DI were not as impaired compared to IH. * p<0.05 vs UH/IA control; # p<0.05 IH vs CH. CONCLUSION IH is a unique paradigm of hypoxic stress that specifically induces insulin resistance and impairs the disposition of glucose into the peripheral tissues. Supported by NHBL063767