Department of Biochemistry, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
Department of Biochemistry, Veritas University, Bwari, Abuja, Nigeria.
Sci Rep. 2021 Sep 21;11(1):18724. doi: 10.1038/s41598-021-98158-7.
Skeletal muscles are important in glucose metabolism and are affected in type 2 diabetes (T2D) and its complications. This study investigated the effect of vanillin on redox imbalance, cholinergic and purinergic dysfunction, and glucose-lipid dysmetabolism in muscles of rats with T2D. Male albino rats (Sprague-Dawley strain) were fed 10% fructose ad libitum for 2 weeks before intraperitoneally injecting them with 40 mg/kg streptozotocin to induce T2D. Low (150 mg/kg bodyweight (BW)) and high (300 mg/kg BW) doses of vanillin were orally administered to diabetic rats. Untreated diabetic rats and normal rats made up the diabetic control (DC) and normal control (NC) groups, respectively. The standard antidiabetic drug was metformin. The rats were humanely put to sleep after 5 weeks of treatment and their psoas muscles were harvested. There was suppression in the levels of glutathione, activities of SOD, catalase, ENTPDase, 5'Nucleotidase and glycogen levels on T2D induction. This was accompanied by concomitantly elevated levels of malondialdehyde, serum creatine kinase-MB, nitric oxide, acetylcholinesterase, ATPase, amylase, lipase, glucose-6-phosphatase (G6Pase), fructose-1,6-biphophastase (FBPase) and glycogen phosphorylase activities. T2D induction further resulted in the inactivation of fatty acid biosynthesis, glycerolipid metabolism, fatty acid elongation in mitochondria and fatty acid metabolism pathways. There were close to normal and significant reversals in these activities and levels, with concomitant reactivation of the deactivated pathways following treatment with vanillin, which compared favorably with the standard drug (metformin). Vanillin also significantly increased muscle glucose uptake ex vivo. The results suggest the therapeutic effect of vanillin against muscle dysmetabolism in T2D as portrayed by its ability to mitigate redox imbalance, inflammation, cholinergic and purinergic dysfunctions, while modulating glucose-lipid metabolic switch and maintaining muscle histology.
骨骼肌在葡萄糖代谢中起着重要作用,并且在 2 型糖尿病(T2D)及其并发症中受到影响。本研究探讨了香草醛对 T2D 大鼠肌肉中氧化还原失衡、胆碱能和嘌呤能功能障碍以及糖脂代谢紊乱的影响。雄性白化大鼠(Sprague-Dawley 品系)在腹腔注射 40mg/kg 链脲佐菌素诱导 T2D 前,自由摄入 10%果糖 2 周。低(150mg/kg 体重(BW))和高(300mg/kg BW)剂量的香草醛经口给予糖尿病大鼠。未治疗的糖尿病大鼠和正常大鼠分别组成糖尿病对照组(DC)和正常对照组(NC)。标准抗糖尿病药物是二甲双胍。治疗 5 周后,将大鼠人道处死并采集其腰大肌。T2D 诱导后,谷胱甘肽水平、SOD、过氧化氢酶、ENTPDase、5'核苷酸酶和糖原水平受到抑制。同时,丙二醛、血清肌酸激酶-MB、一氧化氮、乙酰胆碱酯酶、ATP 酶、淀粉酶、脂肪酶、葡萄糖-6-磷酸酶(G6Pase)、果糖-1,6-二磷酸酶(FBPase)和糖原磷酸化酶活性升高。T2D 诱导还导致脂肪酸合成、甘油脂质代谢、线粒体脂肪酸延长和脂肪酸代谢途径失活。香草醛治疗后,这些活性和水平接近正常并显著逆转,同时失活途径被重新激活,这与标准药物(二甲双胍)相比具有优势。香草醛还显著增加了肌肉的体外葡萄糖摄取。结果表明,香草醛通过减轻氧化还原失衡、炎症、胆碱能和嘌呤能功能障碍,同时调节葡萄糖-脂质代谢转换并维持肌肉组织学,对 T2D 肌肉代谢紊乱具有治疗作用。