Panax notoginseng saponins alleviate skeletal muscle insulin resistance by regulating the IRS1–PI3K–AKT signaling pathway and GLUT4 expression

Abstract

Panax notoginseng saponins ( PNS ) are a commonly used traditional medicine to treat diabetes in China. Recent studies have confirmed their anti‐diabetic effects, but the underlying mechanisms have remained unclear. The present study was designed to explore whether PNS decrease hyperglycemia by improving insulin sensitivity in skeletal muscle and to elucidate the molecular mechanisms. The anti‐diabetic effects of PNS were analyzed in a skeletal myoblast cell line, C2C12, and in high fat diet‐induced diabetic KKA y mice. C2C12 cells were treated with PNS (50, 100, and 200 μg·L −1 ) and examined for glucose uptake, cell viability and expression of components of the phosphoinositide 3‐kinase ( PI 3K)–protein kinase B ( AKT ) signaling pathway. KKA y mice were intraperitoneally injected with PNS (200 mg·kg −1 ) for 6 weeks. Body weight, blood glucose, serum insulin, serum lipid, glucose and insulin tolerance were measured to evaluate the anti‐diabetic effects of PNS . Pathological changes, apoptosis and the PI 3K– AKT signaling pathway were analyzed in KKA y skeletal muscle. PNS significantly increased insulin‐induced glucose uptake, but did not affect the cell viability of C2C12 cells. In addition, PNS reduced blood glucose and serum insulin levels and improved glucose tolerance and insulin tolerance of KKA y mice. Pathological changes and apoptosis of skeletal muscle were relieved by PNS treatment. Moreover, PNS treatment enhanced expression of mRNA encoding IRS 1 and GLUT 4, as well as the protein expression of phosphorylated (p) ‐insulin receptor substrate 1 ( IRS 1), p‐ PI 3K, p‐ AKT and glucose transporter type 4 ( GLUT 4) in C2C12 and KKA y mouse muscle. Collectively, these data indicate that PNS reduces hyperglycemia and insulin resistance through up‐regulating GLUT 4 expression and the IRS 1– PI 3K– AKT signaling pathway. Furthermore, PNS alleviated diabetes skeletal muscle pathological damage. Thus, our data suggest that PNS may be promising anti‐diabetic compounds.

Dynamic changes of blood glucose, serum biochemical parameters and gene expression in response to exogenous insulin in Arbor Acres broilers and Silky fowls

“…Skeletal muscle is responsible for a significant fraction of glucose uptake from the blood stream in the insulin-stimulated state 29 . More than 60% of blood glucose is absorbed by skeletal muscle 30,31 . And in growing broiler chickens, with the rapid increase of skeletal muscle mass, it is likely that glucose uptake by the skeletal muscles increases in importance 32 .…”

Efficiency comparison of PGBR extract and γ‐oryzanol in antioxidative stress and anti‐inflammatory properties against metabolic syndrome

“…Protein extraction procedures were previously described (Boizard et al, ; Bui et al, ; DeFronzo, ; Guo et al, ; Han et al, ; Violletet al, ). In short, tissue samples were homogenized and later quantified using the Pierce BCA Protein Assay Kit (Thermo Fisher Scientific, MA, USA).…”

“…The skeletal muscle is a significant organ for controlling the postprandial glucose consumption and storage under the signaling of insulin. Under metabolic disorders, reports demonstrated that inflammation and oxidative stress impair the insulin signaling to maintain the glucose homeostasis in skeletal muscles (Guo et al, ). In contrast, improving insulin sensitivity of skeletal muscle has been demonstrated to be an effective strategy in controlling blood glucose levels (DeFronzo, ; Smith & Muscat, ).…”

Early high-fat feeding improves histone modifications of skeletal muscle at middle-age in mice

“…Although altered expression of Ppargc1a mRNA in skeletal muscle might be one of causes improve the glucose intolerance in middle-aged mice, the results of the present study showed no changes between Control and High fat groups at 13-mo-old. Insulin receptor substrate IRS1 mediates insulin-derived signal via phosphorylation, which activates its downstream effector, AKT, to cause GLUT4 translocation to the membrane [12]. According to the result showing no change in Irs1 mRNA expression after high fat diet feeding, it was suggested that the level of gene expression was not related to glucose intolerance in skeletal muscle.…”

“…The THUN-DERBIRD qPCR Mix (TOYOBO) was used for PCR reaction following manufacturer-recommended dilution procedures. Genes that are reportedly related to glucose tolerance or type 2 diabetes in skeletal muscle of mice were targeted to analyze the regulation of gene expression [9][10][11][12][13][14][15]. Primer pairs for the gene expression analysis are shown in Table 1.…”