Chertow B S, Webb M D, Leidy J W, Cordle M B
Section of Endocrinology, Marshall University School of Medicine, Huntington, WV.
Res Commun Chem Pathol Pharmacol. 1989 Jan;63(1):27-44.
The cellular effects of retinoids may be relevant to protection against chemical-induced diabetes mellitus. To determine whether retinyl palmitate protects the beta cell from streptozotocin- and alloxan-induced diabetes, we injected streptozotocin, 60 mg/kg, or alloxan, 100 mg/kg, with or without varying doses of retinyl palmitate intraperitoneally or by tail vein. Plasma glucose was measured for over 4 weeks. To determine if the protective effects of retinyl palmitate were mediated through effects on superoxide dismutase, a scavenger of tissue free radicals, we determined whether retinyl palmitate affected islet superoxide dismutase activity. Retinyl palmitate, given intraperitoneally or by tail vein, protected against both streptozotocin- and alloxan-induced diabetes. The effect was dependent on the route of administration. When given intraperitoneally, the protective effect was greater than when given intravenously. When given by tail vein, the protective effect was dose dependent. Retinyl palmitate in vitro did not affect insulin secretion or islet superoxide dismutase. We conclude that retinyl palmitate treatment protects against streptozotocin- and alloxan-induced diabetes. Further studies are needed to determine whether retinyl palmitate protects against the development of diabetes in other animal models and whether this effect is relevant to diabetes in man.
维甲酸的细胞效应可能与预防化学诱导的糖尿病有关。为了确定棕榈酸视黄酯是否能保护β细胞免受链脲佐菌素和四氧嘧啶诱导的糖尿病影响,我们腹腔注射或尾静脉注射60mg/kg链脲佐菌素或100mg/kg四氧嘧啶,同时给予不同剂量的棕榈酸视黄酯。连续4周以上测量血浆葡萄糖水平。为了确定棕榈酸视黄酯的保护作用是否通过对超氧化物歧化酶(一种组织自由基清除剂)的作用介导,我们测定了棕榈酸视黄酯是否影响胰岛超氧化物歧化酶活性。腹腔注射或尾静脉注射棕榈酸视黄酯均能预防链脲佐菌素和四氧嘧啶诱导的糖尿病。这种作用取决于给药途径。腹腔注射时,保护作用大于静脉注射。尾静脉注射时,保护作用呈剂量依赖性。体外实验中,棕榈酸视黄酯不影响胰岛素分泌或胰岛超氧化物歧化酶。我们得出结论,棕榈酸视黄酯治疗可预防链脲佐菌素和四氧嘧啶诱导的糖尿病。需要进一步研究以确定棕榈酸视黄酯是否能预防其他动物模型中的糖尿病发展,以及这种作用是否与人类糖尿病相关。