Background Type 2 diabetes has become one of the most common diseases worldwide, causing a serious social burden. As a first-line treatment for diabetes, metformin can effectively improve insulin resistance. It has been reported that 12α-hydroxylated BA (mainly CA) is associated with insulin resistance. The purpose of this study was to analyze the changes in CA and possible signaling mechanisms in diabetic rats after metformin intervention. Methods HepG2 cells were cultured after adding different concentrations of metformin. The cell viability was measured using CCK8 kit, and the expression of FXR, MAFG, and CYP8B1 in cells was detected by WB. The rat models of type 2 diabetes were induced by low-dose streptozotocin by feeding a high-fat diet, and the control rats (CON) were fed on normal food; the diabetic rats (DM) were given a high-fat diet without supplementation with metformin, while the metformin-treated diabetic rats (DM + MET) were given a high-fat diet and supplemented with metformin. Biochemical parameters were detected at the end of the test. Expression levels of FXR, CYP8B1, and MAFG were assessed by WB. Serum CA were measured using an enzyme-linked immunosorbent assay (ELISA). Results In HepG2 cells, metformin dose-dependently enhanced the transcriptional activity of FXR and MAFG and inhibited the expression of CYP8B1. Metformin-treated DM rats showed improved glucose and bile acid metabolism. In addition, significantly increased FXR and MAFG and decreased CYP8B1 were observed in DM + MET rats. At the same time, the CA content of metformin-treated rats was lower than that of diabetic rats. Conclusion Changes in CA synthesis after metformin treatment may be associated with inhibition of CYP8B1. These results may play an important role in improving insulin sensitivity after metformin treatment.

An intriguing area of research in type 2 diabetes recently discovered association of metformin therapy with thyroid functional and morphological changes. We aimed to evaluate the external symptoms and biochemical indicators concerning thyroid function in rats treated with metformin. Male wistar rats were randomly divided into four groups: Group (D–/M–), Group (D–/M+), Group (D+/M–), and Group (D+/M+), according to whether they were induced to diabetic model or placed on metformin. Characteristics of food intake, body weight, and other external symptoms were recorded. Thyroid function, concluding serum thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), were measured. We found a significantly higher TSH and lower FT4 in rats in Group (D+/M–), compared with rats in Group (D–/M–), but no significant change in FT3 level. Rats on metformin treatment exhibited relatively lower body weight and symptoms like irritability and diarrhea, concomitant with marked increase in FT3 and FT4 , no matter if they were induced to diabetic model or not . A slight but significant reduction in TSH concentration was also observed in rats received metformin. These data reveal that metformin can modify thyroid function with corresponding clinical symptoms of hyperthyroidism in male rats. Metformin's contribution to suppress TSH and increase FT3, FT4 should arise our attention to its treatment interference in clinical practice.