Gestational diabetes mellitus is a frequently diagnosed glucose metabolic disorder during pregnancy. Diabetes mellitus has been found to pose important health risks to the developing fetus, mother, and offspring. Here, we investigated the protective effects of S14G-humanin, a potent humanin analogue, against maternal and neonatal adverse outcomes in mice with diabetes mellitus. The results show that S14G-humanin administration reduced the blood glucose levels and elevated the serum insulin levels in diabetes mellitus mice. The parameters of serum lipid metabolism including low-density lipoprotein, total cholesterol, and high-density lipoprotein in diabetes mellitus mice were also decreased after S14G-humanin administration. Intervention with S14G-humanin also increased the fetus alive ratio and fetal length, as well as decreased fetal and placenta weights. In addition, we demonstrate that S14G-humanin elevated the activity of the anti-oxidative enzymes catalase, glutathione peroxidase, and superoxide dismutase and reduced the inflammatory cytokines levels in the placentas of diabetes mellitus mice. The significantly increased endoplasmic reticulum stress in the placentas of diabetes mellitus mice was also attenuated by S14G-humanin administration. Taken together, S14G-humanin exerted protective roles in improving maternal and neonatal outcomes. Our findings indicate that S14G-humanin might be an effective intervention approach for women with diabetes mellitus.
Keywords: Gestational diabetes mellitus; S14G-humanin; blood glucose; fetal outcome; placenta; serum insulin.