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

Abstract

Aims/Objective The development of type 2 diabetes is a result of insulin resistance in various tissues, including skeletal muscle and liver. Apolipoprotein M (ApoM) plays an important role in the function of high‐density lipoprotein, 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. Materials and Methods The Goto‐Kakizaki (GK) rats were transfected with adeno‐associated virus (AAV) encoding rat ApoM gene or control blank. The oral glucose tolerance test (OGTT) and hyperinsulinemic‐euglycemic clamp (HEC) experiment were used to assess the insulin sensitivity of GK rats. Results The results show that ApoM messenger ribonucleic acid and protein were significantly overexpressed in the pancreatic tissues. Overexpression of ApoM decreased fasting blood glucose and random blood glucose, improved glucose tolerance, and increased bodyweight and insulin levels in GK rats. The glucose infusion rate of rats in the AAV encoding rat ApoM gene group during HEC test was 1.04‐, 1.23‐ and 1.95‐fold higher than that in the AAV control blank group at 1–3 weeks after injection of AAV, respectively. A Wes‐ProteinSimple assay and quantification was carried out to assess phosphorylated protein kinase B/protein kinase B 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 seventh week after AAV injection. Conclusions ApoM overexpression through adeno‐associated virus gene transfer might improve insulin secretion and insulin sensitivity in GK rats.

Sphingolipid Metabolism and Signaling in Skeletal Muscle: From Physiology to Physiopathology

“…In opposite, overexpression of apoM induced an improvement of insulin sensitivity in mice and enhanced muscle Akt phosphorylation (219). Identical results were observed in Goto-Kakizaki Rats (220). Altogether, these studies demonstrate that circulating S1P can exert protecting effects against the development of tissue insulin resistance.…”

Muscle atrophy phenotype gene expression during spaceflight is linked to a metabolic crosstalk in both the liver and the muscle in mice

“…Among these genes, some are already described for their insulin sensitivity. Fabp2, Abcg5, and Abcg8 genes polymorphisms are associated with insulin sensitivity while Apom might protect against insulin resistance ( Gylling et al., 2004 ; Kurano et al., 2020 ; Weiss et al., 2002 ; Yu et al., 2020 ). Interestingly, Sestrin 1 ( Sesn1 ), a well-known regulator of cell metabolism upregulated in longissimus dorsi of BION-M1 mice, was reported as a discriminating gene in both the liver and the quadriceps ( Gambara et al., 2017a ) .…”

Shenmai injection enhances cisplatin-induced apoptosis through regulation of Mfn2-dependent mitochondrial dynamics in lung adenocarcinoma A549/DDP cells

“…Additionally, a WES™ machine (ProteinSimple, San Jose, CA, USA) was used for apoptosis-related protein detection. A549/DDP cells were retreated with SMI at a dose of 13, 20, and 30 mg/mL for 2 h and then incubated with cisplatin for another 24 h. During sample loading, the whole-cell protein samples, sealing solution, anti-Bax, anti-Bcl-2, anti-Cleaved-caspase 3, secondary antibody (ABclonal, Wuhan, China), luminescent solution, and eluent were successively added to the plate according to a set 3 h run procedure [ 17 ] . Data were analyzed using Compass for SW software.…”