Renal dysfunction in a mouse model of GDM is prevented by metformin through MAPKs

Gestational diabetes mellitus (GDM) incidence is increasing worldwide. In the present study, the effects of metformin on high fat diet (HFD)‑induced renal dysfunction were investigated in GDM mice. In addition, the molecular mechanisms underlying metformin function were examined. GDM was induced by feeding pregnant mice a HFD, and mice were treated with two different doses of metformin (300 and 600 mg/kg/day) or PBS between embryonic day 11.5 (E11.5) and E17.5. The pregnant mice at E18.5 were utilized to analyze the effects of metformin on renal dysfunction. Renal function and the protein expression levels of inflammatory cytokines and factors of the mitogen‑activated protein kinase (MAPK) signaling pathway in the kidneys of pregnant mice were assessed by ELISA and western blotting. Data obtained during late pregnancy suggested that metformin significantly decreased body weight and the levels of blood glucose in GDM mice, as assessed by the glucose tolerance test and the homeostatic model assessment for insulin resistance. The levels of microalbumin and serum β2‑microglobulin in GDM mice during late pregnancy were decreased following treatment with metformin. Furthermore, serum levels of interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α, and phosphorylation of MAPK1/3, MAPK14 and MAPK8 in the kidneys were decreased in GDM mice following metformin treatment at E18.5, compared with the untreated GDM group. The present study suggested that inflammation may be associated with renal dysfunction in GDM mice, and that the MAPK signaling pathway may be involved in the protective effect of metformin on renal dysfunction in GDM mice.