Department of Basic Medical Sciences (Biochemistry Section), University of the West Indies, Mona Campus, Jamaica.
Mol Cell Biochem. 2004 Aug;263(1):29-34. doi: 10.1023/B:MCBI.0000041846.99698.5d.
Nitric oxide (NO) is an important bioactive signaling molecule that mediates a variety of normal physiological functions, which, if altered, could contribute to the genesis of many pathological conditions, including diabetes. In this study, we examined the possible diabetogenicity of NO by noting differences in the cellular binding of insulin in dogs treated with the NO donor, S-nitrosoglutathione (GSNO) compared to captopril-treated controls. GSNO administration resulted in an abnormality in glucose metabolism which was attributed to decreased binding of insulin to its receptor on the cell membrane of mononuclear leucocytes, 11.60 ± 0.60% in GSNO-treated dogs compared with 18.10 ± 1.90% in captopril-treated control (p < 0.05). The decreased insulin binding was attributed to decreased insulin receptor sites per cell, 21.43 ± 2.51 × 10(4) in GSNO-treated dogs compared with 26.60 ± 1.57 × 10(4) in captopril-treated controls (p < 0.05). Average affinity analysis of the binding data demonstrated that this decrease in insulin binding was also due to a decrease in average affinity of the receptor on mononuclear leucocytes for insulin. This was evident by a decrease in empty and filled site affinities in GSNO-treated dogs compared with that of captopril-treated dogs (p < 0.05). It appears that GSNO is exerting its effect by decreasing the number of insulin receptor sites and/or decreasing the average receptor affinity. These results provide evidence for a novel role of NO as a modulator of insulin binding and the involvement of NO in the aetiology of diabetes mellitus. (Mol Cell Biochem 263: 29-34, 2004).
一氧化氮（NO）是一种重要的生物活性信号分子，介导多种正常生理功能，其改变可导致许多病理状况的发生，包括糖尿病。在这项研究中，我们通过观察用一氧化氮供体 S-亚硝基谷胱甘肽（GSNO）治疗的狗与用卡托普利治疗的对照狗之间胰岛素在细胞上的结合差异，研究了 NO 的可能致糖尿病作用。GSNO 给药导致葡萄糖代谢异常，这归因于单核白细胞细胞膜上胰岛素受体与胰岛素的结合减少，GSNO 治疗的狗为 11.60±0.60％，而卡托普利治疗的对照狗为 18.10±1.90％（p＜0.05）。胰岛素结合减少归因于每个细胞的胰岛素受体部位减少，GSNO 治疗的狗为 21.43±2.51×10（4），而卡托普利治疗的对照狗为 26.60±1.57×10（4）（p＜0.05）。结合数据的平均亲和力分析表明，这种胰岛素结合减少也是由于单核白细胞上胰岛素受体的平均亲和力降低所致。这可以通过 GSNO 治疗的狗与卡托普利治疗的狗相比，空和满位亲和力降低来证明（p＜0.05）。似乎 GSNO 通过减少胰岛素受体部位的数量和/或降低平均受体亲和力来发挥作用。这些结果为 NO 作为胰岛素结合调节剂的新作用以及 NO 在糖尿病发病机制中的参与提供了证据。（分子细胞生物化学 263：29-34，2004）。
