Effects of Vaspin on Insulin Resistance in Rats and Underlying Mechanisms

Abstract

Insulin resistance (IR) is the main pathogenesis of metabolic syndrome and a shared pathophysiological change in conditions such as diabetes mellitus, adiposity, hypertension, and atherosclerosis. Visceral adipose tissue-derived serpin (Vaspin) is a newly discovered adipocytokine with insulin-sensitizing and anti-inflammatory effects. To examine if vaspin can improve insulin resistance in rats fed a high-fat diet via the insulin receptor substrate/phosphatidylinositol 3 kinase/protein kinase B/glucose transport (IRS/PI3K/Akt/Glut) and inhibitory κB alpha/nuclear factor-kappa B (IκBα/NF-κB) signalling pathways, thirty male Sprague-Dawley (SD) rats were randomly divided into three groups: the normal control group (NC group, n = 10), high-fat diet group (HFD group, n = 10) and vaspin intervention group (HFD + vaspin group, n = 10). Results showed that intervention with vaspin significantly decreased fasting blood glucose (FBG) and fasting insulin (FINS) concentrations in HFD − fed rats without significantly affecting body weight or triglyceride (TG) or total cholesterol (TC) levels. The areas under the intraperitoneal glucose tolerance test (IPGTT) and the insulin tolerance test (ITT) curves were significantly decreased in HFD + vaspin group compared with the HFD group, and the glucose infusion rate (GIR) showed the same trends. Western blot, real-time polymerase chain reaction (RT-PCR) and immunofluorescence staining showed that vaspin could improve insulin resistance in liver, skeletal muscle and adipose tissue by activating the IRS/PI3K/Akt/Glut signalling pathway and inhibiting the IκBα/NF-κB signalling pathway.

Vaspin antagonizes high fat-induced bone loss in rats and promotes osteoblastic differentiation in primary rat osteoblasts through Smad-Runx2 signaling pathway

“…Sakamoto et al [31] examined the effects of vaspin (1μg/kg/day, 14 days, n = 4) treatment on MCT-induced rise in pulmonary arterial hypertension (PA) pressure and RV to body weight ratio (RV/BW), and demonstrated that vaspin significantly attenuate the rise in PA pressure but have no effect on the body weight. While Liu et al [32] showed that a downward trend in body weight could be seen in HFD-fed rats treated with vaspin (320 ng/kg/day, intraperitoneally, n = 10) for 8 weeks except for significantly decreasing fasting blood glucose and fasting insulin concentrations. However, in this study, no statistically significant.in food intake could be seen in rats treated with vaspin.…”

Vaspin promotes insulin sensitivity in elderly muscle and is upregulated in obesity

“…Vaspin-mediated activation of PI3K/AKT has been reported previously in several other cell types, including pancreatic cells (Liu et al 2017), 3T3-L1 preadipocytes (Liu et al 2015) and endothelial progenitor cells . Furthermore, it was recently reported that vaspin promotes the PI3K/AKT signalling pathway leading to increased GLUT4 protein expression in rats fed a high-fat diet (Liu et al 2018) and can improve glucose tolerance in mice . Therefore, our demonstration that vaspin induces activation of PI3K-AKT signalling and increases insulin sensitivity in obese human myotubes is significant.…”

Circulating Adipokine VASPIN Is Associated with Serum Lipid Profiles in Humans

“…VASPIN inhibits KALLIKREIN 7 by a classical serpin mechanism with high specificity and may thereby contribute to improved insulin sensitivity (Heiker et al, , reviewed in Heiker, ). A second potential pathway was described by Jung et al, who propose a model in which VASPIN acts via the PI3 kinase/AKT pathway and ameliorates atherosclerosis (Jung et al, ; Liu et al, ). This finding was further supported by the analysis of Nicholson et al , showing an induction of the PI3 kinase/AKT axis by VASPIN and thereby promoting GLUT4 expression and translocation (Nicholson et al, ).…”