Abstract: Sleep apnea syndrome (SAS) is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), and it is a risk factor for insulin resistance/type 2 diabetes, hypertension, and cardiovascular diseases. However, the mechanisms linking IH and the diseases remain elusive. We used in vitro IH system to expose pancreatic β-cells, adipocytes, hepatocytes, skeletal muscle cells, neuronal cells, enteroendocrine cells, vascular smooth muscle cells, vascular endothelial cells, juxtaglomerular cells, cardiomyocytes to IH or normoxia for analyzing changes of gene expression and the mechanisms. We found that IH induced (1) attenuation of glucose-induced insulin secretion via downregulation CD38, (2) upregulation of adipokines via downregulation of microRNA (miR)-452, (3) upregulation of hepatokine via downregulation of miR-203, (4) upregulation of myokines via OCT1- and NRF2-mediated mechanism, (5) vascular smooth muscle cell proliferation via upregulation of EGF family, (6) upregulation of ESM1 and ICAM-1 in vascular endothelial cells via downregulation of miR-181a1, (7) upregulation of renin in juxtaglomerular cells via downregulation of miR-203, (8) upregulation of catecholamine-metabolizing enzymes in catecholamine synthesizing neuronal cells via downregulation of miR-375, and (9) downregulation of components for the CD38-cyclic ADP-ribose signal system in cardiomyocytes via upregulation of Pten. In SAS, cells throughout the body are exposed to IH, which affects various cells related to diabetes, hypertension, and heart disease, which are complications frequently seen in SAS. We have clarified the effects of IH exposure through molecular biological methods. In the future, it will be important to develop good animal models and use them to develop treatment and prevention methods.
Keywords: diabetes, hypertension, SAS, IH, CD38-cADPR signal system, Reg-Reg receptor system

Biography: Shin Takasawa was born in 1958 in Kashiwazaki, Nigata, Japan. He qualified as a medical doctor at the age of 25 years in Yamagata University and has completed his PhD at the age of 30 years from Tohoku University School of Medicine. He has been engaged in biochemical and molecular biological research on diseases such as diabetes in Tohoku University Graduate School of Medicine as a staff of Department of Biochemistry. In the process, he found cyclic ADP-ribose as a second messenger in glucose-induced insulin secretion from pancreatic β-cells and Reg (regenerating gene)-Reg receptor system in β-cell regeneration. In 2007, he moved to professor & chairman of Department of Biochemistry, Nara Medical University and performed molecular research concerning sleep apnea syndrome (SAS)/intermittent hypoxia (IH). He has published more than 200 papers in reputed journals and has been serving as an editorial board member of Life Sci. & Int. J. Mol. Sci.