ISSN:
1432-0428
Keywords:
Dehydrouramil hydrate hydrochloride
;
alloxan
;
diabetes
;
islets of Langerhans
;
insulin secretion
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Dehydrouramil hydrate hydrochloride (DHU) is an analogue of alloxan which retains the in vivo diabetogenic activity of alloxan but, in contrast to alloxan, is stable in aqueous media at physiological pH. Using rat islets of Langerhans, we have studied the acute effects of DHU on B cell function. Glucose-stimulated insulin release was markedly inhibited by DHU, the concentration of DHU giving 50% inhibition (I50) was 1 mmol/l; this was lowered to 0.5 mmol/1 when the islets were exposed to DHU for 5 min before elevation of glucose concentration. The basis for this change appeared to be a protective effect of glucose, since the inclusion of 3-0-methylglucose during pre-incubation with DHU also attenuated the subsequent inhibition of glucose-stimulated insulin release. The inhibitory effect on glucose-stimulated insulin release of a 5-min exposure to DHU persisted throughout a subsequent 120-min period in the absence of DHU. DHU also inhibited insulin release stimulated by mannose (20 mmol/l) or by 2-ketoisocaproate (20 mmol/l) with I50 of 1 and 0.5 mmol/l respectively. Concentrations of DHU up to 1 mmol/l had no significant effect on islet glucose oxidation or ATP content; 5 mmol/l DHU did not affect the rate of glucose oxidation, but lowered the ATP content by 30% without pre-incubation and by 60% in islets pre-incubated for 5 min with DHU before addition of glucose. Inhibitory effects of DHU were also found on rates of incorporation of [3H]-leucine into insulin plus proinsulin and into total islet protein; however, these parameters were less sensitive to DHU than was insulin release. These effects of DHU were similar to those of alloxan. These data suggest that DHU is an important new tool for studying the mechanism of action of B cell cytotoxic agents; in addition, the fact that DHU is a potential metabolite of uric acid could have relevance to the aetiology of diabetes mellitus.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00253202
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