Protective mechanism of glucose against alloxan-induced beta-cell damage: pivotal role of ATP.
Glucose prevents the development of diabetes induced by alloxan. In the present study, the protective mechanism of glucose against alloxan-induced beta-cell damage was investigated using HIT-T 15 cell, a Syrian hamster transformed beta-cell line. Alloxan caused beta-cell damages with DNA fragmentation, inhibition of glucose-stimulated insulin release, and decrease of cellular ATP level, but all of these beta-cell damages by alloxan were prevented by the presence of 20 mM glucose. Oligomycin, a specific inhibitor of ATP synthase, completely abolished the protective effects of glucose against alloxan-induced cell damage. Furthermore, treatment of nuclei isolated from HIT-T15 cells with ATP significantly prevented the DNA fragmentation induced by Ca2+. The results indicate that ATP produced during glucose metabolism plays a pivotal role in the protection of glucose against alloxan-induced beta-cell damage.
Rho
H W
HW
Department of Biochemistry, School of Medicine and Institute for Medical Science, Chonbuk National University, Chonju, Korea.
Lee
J N
JN
Kim
H R
HR
Park
B H
BH
Park
J W
JW
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D009840:Oligomycins / Q000494:pharmacology
D007328:Insulin; D009840:Oligomycins; D004533:Egtazic Acid; D000496:Alloxan; D000255:Adenosine Triphosphate; D004247:DNA; D005947:Glucose; D002118:Calcium