The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia.
Hearing Therapeutics Department, Ear Science Institute Australia, Queen Elizabeth II Medical Centre, Nedlands, Perth, WA 6009, Australia.
Biomolecules. 2022 Jun 23;12(7):877. doi: 10.3390/biom12070877.
Recent preclinical studies in our laboratory have shown that the bile acid profile is altered during diabetes development and such alteration has been linked to the diabetes-associated inflammatory profile. Hence, this study aimed to investigate if the first-line antidiabetic drug metformin will alter the bile acid profile and diabetes-associated inflammation in a murine model of pre-type 2 diabetes. C57 mice were randomly allocated into three equal groups of eight. Group One was given a low-fat diet (LFD), Group Two was given a high-fat diet (HFD), and Group Three was given an HFD and, upon prediabetes confirmation, daily oral metformin for one month. Blood glucose, glycated haemoglobin, drug concentrations in tissues and faeces, and the inflammatory and bile acid profiles were measured. Metformin showed wide tissue distribution and was also present in faeces. The bile acid profile showed significant alteration due to prediabetes, and although metformin did not completely normalize it, it did exert significant effects on both the bile acid and the inflammatory profiles, suggesting a direct and, to some extent, positive impact, particularly on the diabetes-associated inflammatory profile.
最近我们实验室的临床前研究表明,在糖尿病发展过程中胆汁酸谱发生改变,这种改变与糖尿病相关的炎症特征有关。因此,本研究旨在探讨一线抗糖尿病药物二甲双胍是否会改变 2 型糖尿病前模型中小鼠的胆汁酸谱和糖尿病相关炎症。将 C57 小鼠随机分为三组,每组 8 只。第一组给予低脂饮食(LFD),第二组给予高脂肪饮食(HFD),第三组给予 HFD,并在确认糖尿病前期后,每天给予口服二甲双胍一个月。测量血糖、糖化血红蛋白、组织和粪便中的药物浓度以及炎症和胆汁酸谱。二甲双胍在组织中有广泛的分布,也存在于粪便中。由于糖尿病前期,胆汁酸谱发生了显著改变,尽管二甲双胍没有完全使其正常化,但它确实对胆汁酸和炎症谱都有显著影响,表明其对糖尿病相关炎症谱有直接的、在某种程度上是积极的影响。