Exp Mol Med.  2000 Mar;32(1):12-17.

Protective mechanism of glucose against alloxan-induced beta-cell damage: pivotal role of ATP

• Rho HW
• Lee JN
• Kim HR
• Park BH
• Park JW

Abstract

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.

Keyword

glucose; ATP; alloxan; diabetes; DNA fragmentation

MeSH Terms

Adenosine Triphosphate/pharmacology
Adenosine Triphosphate/metabolism
Alloxan/pharmacology*
Animal
B-Lymphocytes/metabolism
B-Lymphocytes/drug effects*
B-Lymphocytes/cytology
Calcium/pharmacology
Cell Line
Cell Nucleus/genetics
Cell Nucleus/drug effects
Cell Survival
DNA/metabolism
DNA/genetics
DNA/drug effects
DNA Fragmentation
Dose-Response Relationship, Drug
Egtazic Acid/pharmacology
Glucose/pharmacology*
Insulin/secretion
Oligomycins/pharmacology