Apolipoprotein M overexpression through adeno‐associated virus gene transfer improves insulin secretion and insulin sensitivity in Goto‐Kakizaki rats

Abstract

Objective The development of type 2 diabetes as a result of insulin resistance in various tissues, including skeletal muscle and liver. ApoM plays an important role in the function of HDL and also affects hepatic lipid and glucose metabolism. In this study, we aimed to investigate whether apoM overexpression modulates glucose metabolism and improves insulin sensitivity. Methods and results The Goto‐Kakizaki (GK) rats were transfected with adeno‐associated virus (AAV) encoding rat apoM gene (AAV‐apoM group) or control blank (AAV‐NC group). The results show that apoM mRNA and protein were significantly overexpressed in the pancreas tissues. Overexpression of apoM decreased fasting blood glucose and random blood glucose, improved glucose tolerance, and increased body weight and insulin level in GK rats. The glucose infusion rate (GIR) of rats in the AAV‐apoM group during hyperinsulinemic‐euglycemic clamp test was 1.04, 1.23 and 1.95 times higher than that in the AAV‐NC group at 1 to 3 weeks after injection of AAV, respectively. A Wes‐ProteinSimple assay and quantification was performed to assess phosphorylated p‐AKT/AKT protein levels in the muscle tissues of apoM‐overexpressing GK rats, and they were found to be higher than those of the control group at the 7^th week after AAV injection. Conclusion ApoM overexpression via adeno‐associated virus gene transfer may improve insulin secretion and insulin sensitivity in GK rats.