GIP受体抑制剂对诱导的糖尿病小鼠糖脂代谢的研究

摘要

目的 研究糖依赖性胰岛素释放肽(GIP)受体抑制剂pro3(GIP)对高脂饲料和链脲佐菌素诱导的糖尿病小鼠的血糖、血脂、瘦素、脂联素以及脂肪组织炎症的影响.方法 27只小鼠随机分正常组和模型组,模型组喂食高脂饲料并注射链尿佐菌素,血糖≥16.9 mmol/L者共17只,为糖尿病模型组.将模型组分为糖尿病对照组和pro3 (GIP)组,后者给予pro3(GIP)进行干预.每周追踪血糖,并进行糖耐量的测定.取小鼠血清测血脂、瘦素、脂联素,其脂肪组织进行HE染色,观察脂肪组织炎症的变化.结果 药物干预6周后,pro3(GIP)组的血糖较糖尿病组的血糖明显减低,差异有统计学显著性意义(t=8.43,P＜0.01),0,30,60和120min的胰岛素水平也均明显低于糖尿病组(t=3.90,2.60,6.88和3.33,P＜0.05).病理HE染色观察,pro3(GIP)组脂肪组织的炎症浸润较糖尿病组明显减轻,此外pro3 (GIP)组血清瘦素水平显著低于糖尿病组(t=5.04,P＜0.01),但两组的血清三酰甘油、胆固醇及脂联素水平均无明显差异(P＞0.05).结论 pro3(GIP)能显著地降低糖尿病小鼠的血糖、胰岛素、瘦素水平,并减轻脂肪的炎症浸润,进而调节糖尿病小鼠的代谢水平.%Objective To investigate the metabolic effects of glucose dependent insulinotropic peptide receptor antagomst pro3 (GIP) in induced diabetes mice about blood glucose,triglyceride,cholesterol,leptin and fatty issue.Methods 27 C57 mice were randomly divided into normal group and diabetes mice group,and the mice in diabetes group were fed with high fat food and intraperitoneal injected streptozocin.Then 1 mouse that random blood giucose lower than 16.9 mmol/L was deleted in diabetes group.The rest mice in diabetes group were divided into two groups,diabetes control group,pro3 (GIP) group.Pro3 (GIP) group was given drug pro3 (GIP).The bloodglucose and glucose tolerance were measured.After treatment for 6 weeks,all mice were sacrificed and fatty tissues were collected.Results After 6 weeks,the blood glucose of the pro3 (GIP) group was obviously lower than diabetes control group (t=8.43,P＜0.01),and insulin levers in 0,30,60 and 120 min were obviously lower than diabetes control group (t =3.90,2.60,6.88 and 3.33,P＜0.05).There was significant difference between pro3 (GIP) group and diabetes control group about inflammatory cells.Moreover,leptin in pro3 (GIP) group was obviously lower than in diabetes control group (t =5.04,P＜0.01),but triglyceride,cholesterol,and adiponectin had no significant difference between two groups.Conclusion Pro3 (GIP) can significantly reduce blood glucose,insulin level,leptin of diabetes mice,and attenuate the inflammatory cells infiltration in fatty issue.