Oxidative stress and abnormal lipid metabolism in diabetes can trigger renal lipotoxicity, extending to diabetic nephropathy. Vitamin D3 has been known to be involved in lipid metabolism as well as insulin secretion or inflammation. Therefore, we hypothesized that vitamin D3 supplementation attenuated hyperglycemia-induced renal damage in diabetic mice. Diabetes was induced by a 40% kJ high-fat diet with 30 mg/kg body weight of streptozotocin by intraperitoneal injection twice in male C57BL/6J mice. Among diabetic mice (fasting blood glucose > 140 mg/dL), mice were supplemented with 300 ng/kg body weight of vitamin D3 dissolved in olive oil for 12 weeks. Normal control and diabetic control mice were orally administrated with olive oil as a vehicle. Normal control mice were fed with an AIN-93G diet during the experiment. Vitamin D3 supplementation in diabetic mice improved glucose intolerance and kidney function, demonstrated by diminishing glomerular areas. Vitamin D3 supplementation in diabetic mice significantly reduced triglycerides and low-density lipoprotein cholesterol in plasma as well as triglycerides and total cholesterol in the kidney. Furthermore, vitamin D3 supplementation attenuated lipid synthesis, oxidative stress, and apoptosis, accompanied by activation of β-oxidation, antioxidant defense enzymes, and autophagy in diabetic mice. In conclusion, vitamin D3 supplementation ameliorates hyperglycemia-induced renal damage through the regulation of lipid metabolisms, oxidative stress, apoptosis, and autophagy in diabetes. Vitamin D3 could be a promising nutrient to weaken diabetic nephropathy.

中文翻译：

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维生素 D3 可改善糖尿病小鼠的脂肪吞噬相关的肾脏脂质代谢和组织损伤

糖尿病中的氧化应激和脂质代谢异常可引发肾脂毒性，扩展到糖尿病肾病。已知维生素 D3 参与脂质代谢以及胰岛素分泌或炎症。因此，我们假设补充维生素 D3 可以减轻糖尿病小鼠高血糖引起的肾损伤。通过在雄性 C57BL/6J 小鼠中腹腔注射 40% kJ 高脂肪饮食和 30 mg/kg 体重的链脲佐菌素诱导糖尿病。在糖尿病小鼠（空腹血糖 > 140 mg/dL）中，小鼠补充 300 ng/kg 体重溶于橄榄油的维生素 D3 12 周。正常对照和糖尿病对照小鼠口服橄榄油作为载体。在实验过程中，正常对照小鼠喂食 AIN-93G 饮食。在糖尿病小鼠中补充维生素 D3 改善了葡萄糖耐受不良和肾功能，这通过肾小球面积减少来证明。在糖尿病小鼠中补充维生素 D3 可显着降低血浆中的甘油三酯和低密度脂蛋白胆固醇以及肾脏中的甘油三酯和总胆固醇。此外，补充维生素 D3 可减弱糖尿病小鼠的脂质合成、氧化应激和细胞凋亡，同时激活 β-氧化、抗氧化防御酶和自噬。总之，补充维生素 D3 通过调节糖尿病中的脂质代谢、氧化应激、细胞凋亡和自噬来改善高血糖引起的肾损伤。维生素 D3 可能是一种有希望减轻糖尿病肾病的营养素。