BioScience Research Centre and Department of Medicine, Gayatri Vidya Parishad Hospital, GVP College of Engineering Campus, Visakhapatnam 530048, India.
Department of Biotechnology, Gandhi Institute of Science (GIS), GITAM University, Visakhapatnam 530048, India.
Int J Mol Sci. 2021 Feb 3;22(4):1516. doi: 10.3390/ijms22041516.
Type 1 diabetes mellitus is an autoimmune disease characterized by increased production of pro-inflammatory cytokines secreted by infiltrating macrophages and T cells that destroy pancreatic β cells in a free radical-dependent manner that causes decrease or absence of insulin secretion and consequent hyperglycemia. Hence, suppression of pro-inflammatory cytokines and oxidative stress may ameliorate or decrease the severity of diabetes mellitus. To investigate the effect and mechanism(s) of action of RVD1, an anti-inflammatory metabolite derived from docosahexaenoic acid (DHA), on STZ-induced type 1 DM in male Wistar rats, type 1 diabetes was induced by single intraperitoneal (i.p) streptozotocin (STZ-65 mg/kg) injection. RVD1 (60 ng/mL, given intraperitoneally) was administered from day 1 along with STZ for five consecutive days. Plasma glucose, IL-6, TNF-α, BDNF (brain-derived neurotrophic factor that has anti-diabetic actions), LXA4 (lipoxin A4), and RVD1 levels and BDNF concentrations in the pancreas, liver, and brain tissues were measured. Apoptotic (), inflammatory () genes and downstream insulin signaling proteins (Gsk-3β/Foxo1) were measured in the pancreatic tissue along with concentrations of various antioxidants and lipid peroxides. RVD1 decreased severity of STZ-induced type 1 DM by restoring altered plasma levels of TNF-α, IL-6, and BDNF ( < 0.001); expression of pancreatic genes and downstream insulin signaling proteins (Gsk-3β/Foxo1) and the concentrations of antioxidants and lipid peroxides to near normal. RVD1 treatment restored expression of genes, plasma LXA4 ( < 0.001) and RVD1 levels and increased brain, pancreatic, intestine, and liver BDNF levels to near normal. The results of the present study suggest that RVD1 can prevent STZ-induced type 1 diabetes by its anti-apoptotic, anti-inflammatory, and antioxidant actions and by activating the gene that is needed for pancreatic β cell proliferation.
1 型糖尿病是一种自身免疫性疾病，其特征是浸润的巨噬细胞和 T 细胞分泌的促炎细胞因子增加，这些细胞因子以自由基依赖的方式破坏胰腺β细胞，导致胰岛素分泌减少或缺失，从而导致高血糖。因此，抑制促炎细胞因子和氧化应激可能会改善或减轻糖尿病的严重程度。为了研究抗炎代谢产物 RVD1（源自二十二碳六烯酸 (DHA)）对雄性 Wistar 大鼠链脲佐菌素 (STZ)诱导的 1 型糖尿病的作用及其机制，通过单次腹腔内 (i.p) 注射链脲佐菌素 (STZ-65mg/kg) 诱导 1 型糖尿病。从第 1 天开始，每天腹腔内给予 RVD1（60ng/mL），连续 5 天。测量血浆葡萄糖、IL-6、TNF-α、BDNF（具有抗糖尿病作用的脑源性神经营养因子）、LXA4（脂氧素 A4）和 RVD1 水平以及胰腺、肝脏和脑组织中的 BDNF 浓度。还测量了胰腺组织中凋亡 ()、炎症 () 基因和下游胰岛素信号蛋白 (Gsk-3β/Foxo1) 以及各种抗氧化剂和脂质过氧化物的浓度。RVD1 通过恢复 STZ 诱导的 1 型糖尿病改变的血浆 TNF-α、IL-6 和 BDNF 水平（<0.001）来降低其严重程度；表达胰腺基因和下游胰岛素信号蛋白 (Gsk-3β/Foxo1) 以及抗氧化剂和脂质过氧化物的浓度接近正常。RVD1 治疗恢复了基因的表达，增加了血浆 LXA4（<0.001）和 RVD1 水平，并使大脑、胰腺、肠道和肝脏的 BDNF 水平接近正常。本研究结果表明，RVD1 可以通过其抗凋亡、抗炎和抗氧化作用以及通过激活胰腺β细胞增殖所需的基因来预防 STZ 诱导的 1 型糖尿病。
