Elevated cAMP level attenuates 2-deoxy-d-ribose-induced oxidative damage in pancreatic beta-cells.
Glucose toxicity to pancreatic beta-cells is defined as irreversible beta-cell damage, including apoptosis, caused by chronic exposure to high glucose levels in type 2 diabetes. Oxidative stress is an important mechanism for glucose toxicity to pancreatic beta-cells. Reducing sugars produce reactive oxygen species through autoxidation and protein glycosylation. 2-Deoxy-d-ribose (dRib) is a reducing sugar with high reactivity. We investigated whether cAMP-stimulating agents could protect beta-cells from dRib-induced oxidative damage. HIT-T15 cells were cultured with various concentrations of dRib for 24 h. We measured cell survival, intracellular cAMP and H2O2 levels, and apoptosis. dRib decreased cell survival in a dose- and time-dependent manner and markedly increased intracellular H2O2 levels and apoptosis. N-Acetyl-l-cysteine decreased dRib-induced rises in intracellular H2O2 and apoptosis to control levels. Forskolin, IBMX, and dbcAMP markedly elevated intracellular cAMP levels and significantly attenuated dRib-induced cytotoxicity and apoptosis, but had no influence on the dRib-induced rise in intracellular H2O2 levels. These results demonstrate that dRib produced oxidative stress and apoptosis in pancreatic beta-cells and that elevated intracellular cAMP levels reduced dRib-induced damage, independent of reactive oxygen species metabolism.
Koh
Gwanpyo
G
Department of Endocrinology and Metabolism, Kyung Hee University College of Medicine, 1 Hoegi-dong, Dongdaemoon-gu, Seoul 130-702, Republic of Korea.
Suh
Kwang Sik
KS
Chon
Suk
S
Oh
Seungjoon
S
Woo
Jeong-taek
JT
Kim
Sung-Woon
SW
Kim
Jin-Woo
JW
Kim
Young-Seol
YS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism*; D003855:Deoxyribose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000502:physiology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*
D003855:Deoxyribose; D000242:Cyclic AMP