Department of Physiology and Biophysics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Marine Living Sciences, Iranian National Institute for Oceanography and Atmospheric Sciences (INIOAS), Tehran, Iran.
Iran J Basic Med Sci. 2015 Feb;18(2):115-21.
Some pathologic situations such as diabetes and metabolic syndrome are associated with alternation in nitric oxide level. Incidence of these condition increases with aging. On the other hand, insulin secretion is modulated by nitric oxide, and nitric oxide synthase (NOS) activity is also altered in diabetes. In this study, modification in the enzyme activity associated with aging and also optimized procedure for islet NOS assay was investigated.
Male Wistar rats were randomly divided in two experimental groups: A: adult rats; were 4 month old and B: old rats; were 12 month old. In all groups, plasma glucose, insulin and NOX (nitrite + nitrate = NOX) were measured, and also insulin secretion in isolated pancreatic islet with or without L-NAME was investigated. Furthermore, the inducible NOS activity with L-citrulline measurement in islets was measured.
L-citrulline was quantified using one step HPLC column. Aging induced hyperglycemia (P<0.05) and excess plasma NOX (17.74 ± 1.664 and 26.25 ± 2.166 μmol/l in A and B groups respectively, P<0.05) with unaltered plasma insulin. Islet insulin secretion was significantly reduced in aging rats. L-NAME induced islet insulin secretion especially in aging rats (P=0.003). Inducible NOS activity in islets of aging rats was significantly higher than adult rats (1.082 ± 0.084 and 6.277 ± 0.475 pmol/min per mg protein in adult and aging rats, respectively, P<0.001).
These findings show that decreased in islet insulin secretion may be related to increase in iNOS activity in islets, which follows impaired carbohydrate metabolism in aging.
一些病理情况,如糖尿病和代谢综合征,与一氧化氮水平的改变有关。这些情况的发病率随着年龄的增长而增加。另一方面,胰岛素分泌受一氧化氮调节,糖尿病患者的一氧化氮合酶(NOS)活性也发生改变。在这项研究中,我们研究了与衰老相关的酶活性的变化,以及胰岛 NOS 测定的优化程序。
雄性 Wistar 大鼠随机分为两组:A:成年大鼠;4 个月大;B:老年大鼠;12 个月大。在所有组中,测量血浆葡萄糖、胰岛素和 NOX(硝酸盐+亚硝酸盐=NOX),并研究分离的胰岛在有无 L-NAME 存在下的胰岛素分泌情况。此外,还测量了胰岛中诱导型 NOS 活性与 L-瓜氨酸的关系。
使用一步 HPLC 柱定量 L-瓜氨酸。衰老引起高血糖(P<0.05)和过量的血浆 NOX(A 组和 B 组分别为 17.74 ± 1.664 和 26.25 ± 2.166 μmol/L,P<0.05),而血浆胰岛素没有改变。衰老大鼠的胰岛胰岛素分泌明显减少。L-NAME 诱导的胰岛胰岛素分泌在衰老大鼠中尤其明显(P=0.003)。衰老大鼠胰岛中的诱导型 NOS 活性明显高于成年大鼠(分别为 1.082 ± 0.084 和 6.277 ± 0.475 pmol/min/mg 蛋白,P<0.001)。
这些发现表明,胰岛胰岛素分泌减少可能与胰岛中 iNOS 活性增加有关,这与衰老时碳水化合物代谢受损有关。