EFFECTS OF METFORMIN ON SERUM INFLAMMATORY CYTOKINES, INSULIN RESISTANCE, LIPID METABOLISM AND RENAL INJURY IN MICE WITH GESTATIONAL DIABETES MELLITUS

Lingling Wang¹, Huilin Su^{2, *}

¹Second Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410000, Hunan Province, China - ²Department of Obstetrics, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410000, Hunan Province, China

Objective: To explore the effect of metformin on inflammatory cytokines, insulin resistance, lipid metabolism and renal function injury in a mouse model of gestational diabetes mellitus (GDM). 

Methods: Forty-five healthy female C57BL/6J mice were selected and randomly divided into three groups according to the random number table method: control group (no treatment, n=15), GDM group (induced GDM model, n=15) and intervention group (induced GDM model treated with metformin solution, n=15). The mice in the control and GDM groups were fed with PBS solution while the intervention group was treated with metformin until the 17th day of pregnancy. The pregnant mice were placed in a metabolic cage to collect urine, and cardiac blood was collected after the mice were sacrificed under anaesthesia. The serum inflammatory cytokines [interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)], β2-microglobulin (β2-MG), fasting insulin and urinary microprotein level in all mice of each group were determined by enzyme-linked immunosorbent assay (ELISA). In addition, the blood samples from pregnant mice in each group were dropped on blood glucose test strips to observe and record fasting blood glucose (FBG) and the insulin resistance index (HOMA-IR) was calculated using the HOMA homeostasis model. Moreover, the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were measured with a fully automatic analyser. 

Results: Compared with the control group, serum IL-6, TNF-α, FBG, fasting serum insulin (FINS), HOMA-IR, TC, TG, LDL, urinary microprotein and serum β2-MG levels were significantly increased and HDL levels were significantly decreased in the GDM group (P<0.05), and the differences in IL-6, TNF-α, FBG, FINS, HOMA-IR, TC, TG, LDL, urinary microprotein and serum β2-MG levels were not statistically significant between the control and intervention groups (P>0.05). In the intervention group, the levels of serum IL-6, TNF-α, FBG, FINS, TC, TG, LDL, urinary microprotein and serum β2-MG significantly decreased, while the level of HDL significantly increased (P<0.05), compared to the GDM group. 

Conclusion: Metformin can reduce the level of serum inflammatory factors, reverse the increase in insulin resistance and improve the abnormality of lipid metabolism and renal function in GDM mice.