Diabetic dyslipidemia, a common pattern of lipid abnormalities associated with diabetes, is characterized by hyperglycemia, elevated serum levels of triglycerides and low-density lipoprotein (LDL)-cholesterol, and reduced serum levels of high-density lipoprotein (HDL)-cholesterol. These lipid abnormalities make diabetes an independent risk-factor for the development of cardiovascular disease. Two mouse models of diabetes were used in the present study: 1) streptozotocin (STZ)-induced insulin-deficient male Swiss Webster mice (a model of T1DM), and 2) male diet-induced obese (DIO) mice rendered insulin-resistant by maintenance on a high-fat diet for 30 weeks (a model of T2DM). Both models were then treated with MA-[D-Leu-4]-OB3 by oral gavage for 14 or 17 days. At the end of the test period, the mice were exsanguinated by cardiac puncture; serum was prepared from the whole blood and analyzed by ELISA for total-, HDL-, LDL/VLDL-cholesterol, and triglyceride content. In mouse models of both T1DM and T2DM, MA-[D-Leu-4]-OB3 significantly (P < 0.05) reduced serum levels of triglycerides and LDL/VLDL-cholesterol, and elevated serum HDL-cholesterol to levels approaching or equivalent to those seen in normal non-diabetic mice of the same age and sex. Our results suggest that in addition to its effects on energy balance, glycemic control, and cognitive function, MA-[D-Leu-4]-OB3, by modulating serum lipid levels, may also be beneficial in reducing the risk of adverse cardiovascular events associated with both T1DM and T2DM.

糖尿病性血脂异常是与糖尿病相关的脂质异常的常见模式，其特征在于高血糖症，甘油三酸酯和低密度脂蛋白（LDL）-胆固醇的血清水平升高以及高密度脂蛋白（HDL）-胆固醇的血清水平降低。这些脂质异常使糖尿病成为心血管疾病发展的独立危险因素。本研究使用了两种糖尿病小鼠模型：1）链脲佐菌素（STZ）诱导的胰岛素缺乏型雄性Swiss Webster小鼠（T1DM模型），以及2）雄性饮食诱导的肥胖（DIO）小鼠使胰岛素抵抗维持高脂饮食30周（T2DM模型）。然后通过管饲法用MA- [D-Leu-4] -OB3处理两个模型14或17天。在测试期结束时，通过心脏穿刺使小鼠放血。从全血中制备血清，并通过ELISA分析总胆固醇，HDL胆固醇，LDL / VLDL胆固醇和甘油三酸酯的含量。在T1DM和T2DM小鼠模型中，MA- [D-Leu-4] -OB3显着（P <0.05）降低了甘油三酸酯和LDL / VLDL-胆固醇的血清水平，并将血清HDL-胆固醇升高至接近或等同于在相同年龄和性别的正常非糖尿病小鼠中观察到的那些。我们的结果表明，MA- [D-Leu-4] -OB3除了对能量平衡，血糖控制和认知功能有影响外，还可以通过调节血脂水平来降低心血管不良事件的风险。与T1DM和T2DM相关联。MA- [D-Leu-4] -OB3显着（P <0.05）降低了甘油三酸酯和LDL / VLDL-胆固醇的血清水平，并使HDL-胆固醇的水平升高至接近或等同于正常非糖尿病小鼠的水平相同的年龄和性别。我们的结果表明，MA- [D-Leu-4] -OB3除了对能量平衡，血糖控制和认知功能有影响外，还可以通过调节血脂水平来降低心血管不良事件的风险。与T1DM和T2DM相关联。MA- [D-Leu-4] -OB3显着（P <0.05）降低了甘油三酸酯和LDL / VLDL-胆固醇的血清水平，并使血清HDL-胆固醇升高至接近或等同于正常非糖尿病小鼠的水平相同的年龄和性别。我们的结果表明，MA- [D-Leu-4] -OB3除了对能量平衡，血糖控制和认知功能有影响外，还可以通过调节血脂水平来降低心血管不良事件的风险。与T1DM和T2DM相关联。