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.
Highlights
Chemical compounds that selectively damage the pancreatic β-cells constitute a class of diabetogenic drugs (Fischer, 1985)
Our results showed that alloxan-induced β-cell damage is due to the deoxyribonucleic acid (DNA) fragmentation by alloxan, which was significantly inhibited in the presence of glucose
Okamoto (1985) proposed that reactive oxygen species produced from alloxan cause DNA strand breaks, and the damaged DNA activates nuclear poly(ADP-ribose) synthetase, which depletes the cellular pool of NAD+, resulting in β-cell damage
Summary
Chemical compounds that selectively damage the pancreatic β-cells constitute a class of diabetogenic drugs (Fischer, 1985). Our previous studies showed that pretreatment of rats with Ca2+-antagonists such as lanthanum and verapamil completely prevented hyperglycemia induced by alloxan (Kim et al, 1991), and alloxan caused the increase of cytosolic free Ca2+ in rat pancreatic β-cells (Kim et al, 1994), suggesting that Ca2+ plays an important role in the diabetogenesis of alloxan. Since the initial report of Sen & Bhattachaya (1952), it is well established that glucose prevents the development of alloxan-induced β-cell damage in vivo (Scheynius & Taljedal, 1971; Jansson & Sandler, 1988) and in vitro (Malaisse, 1982). This protection of glucose against alloxan-induced β-cell damage is mediated through the metabolism of glucose within the pancreatic β-cells
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