title: Intermittent hypoxia exacerbates pancreatic β-cell dysfunction in a mouse model of diabetes mellitus.
abstract: OBJECTIVE
  The effects of intermittent hypoxia (IH) on pancreatic function in the presence of diabetes and the underlying mechanisms are unclear. We hypothesized that IH would exacerbate pancreatic β-cell dysfunction and alter the fatty acids in the male Tallyho/JngJ (TH) mouse, a rodent model of type 2 diabetes.
  
  
  METHODS
  TH mice were exposed for 14 d to either 8 h of IH or intermittent air (IA), followed by an intraperitoneal glucose tolerance test (IPGTT) and tissue harvest. The effect of IH on insulin release was determined by using a β3-adrenergic receptor (AR) agonist.
  
  
  RESULTS
  During IH, pancreatic tissue pO2 decreased from 20.4 ± 0.9 to 5.7 ± 2.6 mm Hg, as determined by electron paramagnetic resonance oximetry. TH mice exposed to IH exhibited higher plasma glucose levels during the IPGTT (P < 0.001) while the insulin levels tended to be lower (P = 0.06). Pancreatic islets of the IH group showed an enhancement of the caspase-3 staining (P = 0.002). IH impaired the β-AR agonist-mediated insulin release (P < 0.001). IH increased the levels of the total free fatty acids and saturated fatty acids (palmitic and stearic acids), and decreased levels of the monounsaturated fatty acids in the pancreas and plasma. Ex vivo exposure of pancreatic islets to palmitic acid suppressed insulin secretion and decreased islet cell viability.
  
  
  CONCLUSIONS
  Intermittent hypoxia increases pancreatic apoptosis and exacerbates dysfunction in a polygenic rodent model of diabetes. An increase in free fatty acids and a shift in composition towards long chain saturated fatty acid species appear to mediate these effects.
authors.affiliation: Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH ; Dorothy M. Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH.
authors.forename: Shariq I
authors.initials: SI
authors.lastname: Sherwani
authors.forename: Carolyn
authors.initials: C
authors.lastname: Aldana
authors.forename: Saif
authors.initials: S
authors.lastname: Usmani
authors.forename: Christopher
authors.initials: C
authors.lastname: Adin
authors.forename: Sainath
authors.initials: S
authors.lastname: Kotha
authors.forename: Mahmood
authors.initials: M
authors.lastname: Khan
authors.forename: Timothy
authors.initials: T
authors.lastname: Eubank
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.forename: Narasimham
authors.initials: N
authors.lastname: Parinandi
authors.forename: Ulysses J
authors.initials: UJ
authors.lastname: Magalang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000097:blood / Q000502:physiology; D005951:Glucose Tolerance Test; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin
keywords: Intermittent hypoxia; diabetes mellitus; fatty acids; β-cell function