The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus

• Published in: Pharmacological research 2022-01, Vol.175, p.105987, Article 105987
• Main Authors: Yin, Yadong, Pan, Yihui, He, Jin, Zhong, Hong, Wu, Yangyang, Ji, Chenbo, Liu, Lan, Cui, Xianwei
• Format: Article
• Language: English
• Subjects: Adiponectin - blood; Animals; Birth Weight - drug effects; Blood Glucose - drug effects; Cell Line; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - drug therapy; Diabetes, Gestational - blood; Diabetes, Gestational - drug therapy; Female; GDM; Hyperglycemia - blood; Hyperglycemia - drug therapy; Insulin - blood; Insulin Resistance; Insulin-Secreting Cells - drug effects; Mice; Mice, Inbred C57BL; Mitochondrial Proteins - therapeutic use; MOTS-c; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Pregnancy; Skeletal muscle; β-cell
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2021.105987

The most common complication during pregnancy, gestational diabetes mellitus (GDM), can cause adverse pregnancy outcomes and result in the mother and infant having a higher risk of developing type 2 diabetes after pregnancy. However, existing therapies for GDM remain scant, with the most common being lifestyle intervention and appropriate insulin treatment. MOTS-c, a mitochondrial-derived peptide, can target skeletal muscle and enhance glucose metabolism. Here, we demonstrate that MOTS-c can be an effective treatment for GDM. A GDM mouse model was established by short term high-fat diet combined with low-dose streptozotocin (STZ) treatment while MOTS-c was administrated daily during pregnancy. GDM symptoms such as blood glucose and insulin levels, glucose and insulin tolerance, as well as reproductive outcomes were investigated. MOTS-c significantly alleviated hyperglycemia, improved insulin sensitivity and glucose tolerance, and reduced birth weight and the death of offspring induced by GDM. Similar to a previous study, MOTS-c also could activate insulin sensitivity in the skeletal muscle of GDM mice and elevate glucose uptake in vitro. In addition, we found that MOTS-c protects pancreatic β-cell from STZ-mediated injury. Taken together, our findings demonstrate that MOTS-c could be a promising strategy for the treatment of GDM. [Display omitted] •Circulating MOTS-c levels are decreased in women with GDM.•MOTS-c relieves GDM symptoms in a GDM mouse model.•MOTS-c enhances insulin sensitivity in skeletal muscle.•MOTS-c protects pancreatic β-cells from STZ-induced injury.