Department of Physiology, Institute for Biological Research, Sinisa Stanković, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
Nitric Oxide. 2010 Aug 1;23(1):42-50. doi: 10.1016/j.niox.2010.04.001. Epub 2010 Apr 18.
Metabolic abnormalities underlying diabetes can be abrogated by L-arginine. Here we examined the molecular basis of disturbed interscapular brown adipose tissue (IBAT) thermogenesis and the possible role of nitric oxide (NO) in the IBAT of diabetic rats. To induce diabetes, adult Mill Hill hybrid hooded male rats were given a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were further divided into three subgroups receiving: (i) L-arginine.HCl (2.25%) or (ii) N(omega)-nitro-L-arginine methyl ester (L-NAME.HCl, 0.01%) for 12 days in drinking water and (iii) untreated controls. Treatment of the diabetic animals started after diabetes induction (glucose level 12 mmol/L). Diabetes led to a decrease in the mRNA levels of uncoupling protein 1 (UCP1), peroxisomal proliferator activator receptor gamma (PPARgamma) and endothelial NO synthase (eNOS) as revealed by RT-PCR. The diabetic rats had reduced eNOS and inducible NOS (iNOS) protein contents accompanied by low tissue vascularization, a parameter directly related to tissue thermogenic state. Downregulation of glutathione peroxidase (GSH-Px) and catalase (CAT) transcripts were also observed in diabetes. In contrast, the expression level of PPARgamma coactivator-1alpha (PGC-1alpha) mRNA was elevated. Supplementation with L-arginine not only restored diabetes-induced changes in the expressions of these molecules important for IBAT regulation, but also increased the vascularity. Interestingly, L-NAME induced similar patterns of changes in vascularity and PGC-1alpha mRNA level as did l-arginine. In summary, our results provide insight into the molecular basis underlying diabetes-induced metabolic and functional disturbances in the IBAT and suggest a beneficial role for the L-arginine-NO production pathway.
精氨酸可消除糖尿病的代谢异常。在这里，我们研究了肩胛间棕色脂肪组织（IBAT）产热紊乱的分子基础以及一氧化氮（NO）在糖尿病大鼠 IBAT 中的可能作用。为了诱导糖尿病，成年 Mill Hill 杂种 Hooded 雄性大鼠单次给予安妥明剂量（120mg/kg）。非糖尿病组和糖尿病组进一步分为三个亚组，分别接受：（i）精氨酸盐酸盐（2.25%）或（ii）Nω-硝基-L-精氨酸甲酯（L-NAME.HCl，0.01%）在饮用水中 12 天，以及（iii）未经处理的对照组。糖尿病动物的治疗始于糖尿病诱导后（血糖水平 12mmol/L）。RT-PCR 显示，糖尿病导致解偶联蛋白 1（UCP1）、过氧化物酶体增殖物激活受体γ（PPARγ）和内皮型一氧化氮合酶（eNOS）的 mRNA 水平降低。糖尿病大鼠的 eNOS 和诱导型 NOS（iNOS）蛋白含量降低，伴随组织血管化减少，这是与组织产热状态直接相关的参数。还观察到糖尿病时谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）转录物的下调。相比之下，PPARγ共激活剂-1α（PGC-1α）mRNA 的表达水平升高。补充精氨酸不仅恢复了糖尿病诱导的这些对 IBAT 调节重要的分子的表达变化，还增加了血管化。有趣的是，L-NAME 诱导的血管化和 PGC-1α mRNA 水平的变化模式与精氨酸相似。总之，我们的结果提供了对糖尿病诱导的 IBAT 代谢和功能紊乱的分子基础的深入了解，并表明 L-精氨酸-NO 产生途径具有有益作用。
