Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down-regulation of CD38

• Published in: Life sciences (1973) 2012-01, Vol.90 (5-6), p.206-211
• Main Authors: Ota, Hiroyo, Tamaki, Shinji, Itaya-Hironaka, Asako, Yamauchi, Akiyo, Sakuramoto-Tsuchida, Sumiyo, Morioka, Takashi, Takasawa, Shin, Kimura, Hiroshi
• Format: Article
• Language: English
• Subjects: ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1 - metabolism; Animals; ATP-Binding Cassette Transporters - metabolism; body mass index; Calcium Channels, L-Type - metabolism; CD38; Cell Hypoxia - drug effects; Cells, Cultured; Cricetinae; Cyclic ADP-ribose; Diabetes Mellitus, Type 2 - metabolism; enzyme-linked immunosorbent assay; gene expression; Gene Expression - drug effects; geographic information systems; glucokinase; Glucokinase - metabolism; Glucose - pharmacology; Glucose Intolerance - metabolism; Glucose Transporter Type 2 - metabolism; glucose transporters; Glucose-induced insulin secretion; hamsters; Humans; hypoxia; Hypoxia - metabolism; insulin; Insulin - metabolism; insulin resistance; Insulin Secretion; Insulin-Secreting Cells - metabolism; Intermittent hypoxia; islets of Langerhans; Male; Membrane Glycoproteins - metabolism; messenger RNA; noninsulin-dependent diabetes mellitus; normoxia; oxygen; Oxygen - pharmacology; Potassium Channels, Inwardly Rectifying - metabolism; quality of life; Rats; Rats, Wistar; Receptors, Drug - metabolism; reporter genes; reverse transcriptase polymerase chain reaction; sleep; sleep apnea; Sleep apnea syndrome; Sleep Apnea Syndromes - metabolism; Sulfonylurea Receptors; transcription (genetics); transfection; waist circumference
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2011.11.011

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 type2 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. HIT-T15 hamster β-cells and isolated rat islets were exposed to 64 cycles/24h of IH (5min hypoxia/10min normoxia) or normoxia for 24h. Changes of GIS and gene expression in IH-treated β-cells were analyzed by ELISA and real-time RT-PCR, respectively. 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. These results indicate that IH stress directly attenuates GIS from β-cells via the down-regulation of CD38.