title: Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down-regulation of CD38.
abstract: OBJECTIVE
  Sleep apnea syndrome (SAS) is characterized by recurrent episodes of oxygen desaturation during sleep, the development of daytime sleepiness, and deterioration in the quality of life. Accumulating evidence suggests the association of intermittent hypoxia (IH), a hallmark of SAS, and type 2 diabetes independently on body mass index and waist circumference. In addition to insulin resistance, the progression to type 2 diabetes is dependent on the impairment of glucose-induced insulin secretion (GIS) from pancreatic β-cells. However, the direct effects of IH on GIS are elusive.
  
  
  METHODS
  HIT-T15 hamster β-cells and isolated rat islets were exposed to 64 cycles/24 h of IH (5 min hypoxia/10 min normoxia) or normoxia for 24 h. Changes of GIS and gene expression in IH-treated β-cells were analyzed by ELISA and real-time RT-PCR, respectively.
  
  
  RESULTS
  After IH treatment, GIS both from IH-treated HIT-T15 cells and isolated rat islets were significantly attenuated. The level of insulin mRNA was unchanged by IH. The mRNA levels of glucose transporter 2 (Glut2), glucokinase (GK), sulfonylurea receptor1 (SUR1), and L-type Ca2+channel1.2 (Cav1.2) in IH-treated-islets were similar to those in normoxia-treated islets. In contrast, the mRNA level of CD38 in IH-treated islets was significantly lower than that in normoxia-treated islets. The reporter gene assay revealed that the transcription of CD38 was attenuated by IH, and the transfection of CD38 expression vector recovered the attenuation of GIS by IH.
  
  
  CONCLUSIONS
  These results indicate that IH stress directly attenuates GIS from β-cells via the down-regulation of CD38.
authors.affiliation: Second Department of Internal Medicine, Nara Medical University, Kashihara 634-8521, Japan.
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Ota
authors.forename: Shinji
authors.initials: S
authors.lastname: Tamaki
authors.forename: Asako
authors.initials: A
authors.lastname: Itaya-Hironaka
authors.forename: Akiyo
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Sakuramoto-Tsuchida
authors.forename: Takashi
authors.initials: T
authors.lastname: Morioka
authors.forename: Shin
authors.initials: S
authors.lastname: Takasawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D018149:Glucose Intolerance / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000378:metabolism; D012891:Sleep Apnea Syndromes / Q000378:metabolism*; D064233:Sulfonylurea Receptors
chemical_list: C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; C577509:Abcc8 protein, rat; D020746:Calcium Channels, L-Type; D051273:Glucose Transporter Type 2; D007328:Insulin; C419385:L-type calcium channel alpha(1C); D008562:Membrane Glycoproteins; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; C495683:Slc2a2 protein, rat; D064233:Sulfonylurea Receptors; D005941:Glucokinase; D036541:ADP-ribosyl Cyclase; C498156:Cd38 protein, rat; D051997:ADP-ribosyl Cyclase 1; D005947:Glucose; D010100:Oxygen