Comparison of inhibition of glucose-stimulated insulin secretion in rat islets of langerhans by streptozotocin and methyl and ethyl nitrosoureas and methanesulphonates

被引:47
作者
Delaney, CA
Dunger, A
DiMatteo, M
Cunningham, JM
Green, MHL
Green, IC
机构
[1] UNIV SUSSEX,MRC,CELL MUTAT UNIT,BRIGHTON BN1 9RR,E SUSSEX,ENGLAND
[2] UNIV SUSSEX,SCH BIOL SCI,DEPT BIOCHEM,BRIGHTON BN1 9QG,E SUSSEX,ENGLAND
[3] UNIV GREIFSWALD,INST DIABET,KARLSBURG,GERMANY
关键词
insulin secretion; streptozotocin; N-methyl-N-nitrosourea; N-ethyl-N-nitrosourea; methyl methanesulphonate; ethyl methanesulphonate; islets of Langerhans; nitric oxide; O-6-methylguanine; O-6-ethylguanine; oxyhaemoglobin;
D O I
10.1016/0006-2952(95)02102-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We have studied inhibition of glucose-stimulated insulin secretion in islets of Langerhans isolated from adult Sprague-Dawley rats and treated with different alkylating agents. Streptozotocin (STZ), N-methyl-N-nitrosourea (MNU), and N-ethyl-N-nitrosourea (ENU) all released nitric oxide, as demonstrated by an increase in medium nitrite and cellular cyclic GMP. Methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS), which do not possess a nitroso group, did not show evidence of nitric oxide release. All five compounds, however, decreased glucose-stimulated insulin release, suggesting that nitric oxide release was not necessary for the inhibition of secretion. Lack of involvement of nitric oxide was further suggested by the failure of oxyhaemoglobin to reverse STZ and MNU inhibition of insulin secretion. Since ENU was at least as effective as MNU in inhibiting insulin secretion, it appears that alkylation of DNA at the O-6 position of guanine may not be involved in this process.
引用
收藏
页码:2015 / 2020
页数:6
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