Pollen Typhae total flavone improves insulin-induced glucose uptake through the β-arrestin-2-mediated signaling in C2C12 myotubes

Abstract

Defects in insulin-stimulated glucose uptake in skeletal muscle result from the dysfunction of insulin signaling including the phosphatidylinositol-3 kinase (PI3K) pathway and a novel β-arrestin-2-mediated signaling, which leads to insulin resistance (IR). Pollen Typhae, a Chinese herb, has been used for thousands of years in traditional Chinese medicine, and has the potential to inhibit the development of IR. We have previously reported that Pollen Typhae total flavone (PTF), the extract from Pollen Typhae, ameliorates high-glucose- and high-insulin-induced impairment of glucose uptake in 3T3-L1 adipocytes, but the mechanisms remain unclear. The objective of this study was to investigate the effects of PTF on glucose uptake, and to explore the underlying mechanisms in C2C12 myotubes. PTF improved insulin-stimulated glucose uptake in a dose- and time-dependent manner in C2C12 myotubes, and prevented palmitate-induced IR. Furthermore, PTF enhanced the basal gene expression of Src and Akt2, elevated the protein expression of β-arrestin-2, Src and Akt, increased the phosphorylation of insulin receptor-β at Tyr1150/1151 and Akt at Thr308/Ser473 in an insulin-dependent manner, but had no effects on the protein expression of PI3K-p85 or the activity of PI3K. Inhibition of Src but not PI3K restrained PTF-induced phosphorylation of Akt and glucose uptake. Our findings indicate that PTF improves insulin-induced glucose uptake via the β-arrestin-2-mediated signaling in C2C12 myotubes.

Pollen Typhae total flavone improves insulin resistance in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats

“…We have reported that free fatty acid (palmitate) contributes to insulin resistance 15) and that PTF prevents palmitate-induced impairment of glucose uptake in C2C12 myotubes. 6) Interestingly, rosiglitazone also obviously reduced TG and LDL-c levels, which was in accordance with PTF and the past reports. 7,16) At present, although thiazolidinediones, the agonists of peroxisome proliferator-activated receptors-γ such as rosiglitazone and pioglitazone, have been widely used to treat type 2 diabetes, some deleterious side effects including weight gain, and increasing risk of CVD in type 2 diabetes patients also coexist.…”

“…19) Because of the improvement of insulin sensitivity and few side effects, it is likely that PTF is a potential choice for the treatment of type 2 diabetes. We have reported that PTF improves insulin resistance involving the β-arrestin-2-mediated signaling in C2C12 myotubes, 6) which is different from rosiglitazone that mainly activates peroxisome proliferator-activated receptors-γ referring to the phosphatidylinositol-3 kinase (PI3K) insulin signal pathway. 20) Fig.…”

“…Researches show that the components of Pollen Typhae are flavones, unsaturated fatty acids, and so on. [4][5][6] Our recent study has revealed that Pollen Typhae total flavone (PTF), the extract from Pollen Typhae, enhances glucose uptake in C2C12 myotubes in vitro, suggesting the potential action of PTF in ameliorating insulin resistance.…”

Moist exposed burn ointment promotes cutaneous excisional wound healing in rats involving VEGF and bFGF

“…The protein expression of VEGF and bFGF in granulation tissue from eight-day-old wounds was determined by western blotting, as previously described with certain modifications (37). Briefly, tissue homogenates from wound granulation were prepared using RIPA lysis buffer.…”

Effects of <i>Pollen Typhae</i> Total Flavone On &#946;-Arrestin-2/SRC/ AKT signaling in adipose tissues of Type 2 diabetic rats

“…Pollen Typhae has been widely used to treat type 2 diabetes and other diseases characterized by insulin resistance such as metabolic syndrome and non-alcohol fatty liver disease in China. We have ever reported that Pollen Typhae total flavone (PTF), the extract from Pollen Typhae which mainly contains typhaneoside and other constituents (Feng et al 2012a), ameliorates insulin resistance in type 2 diabetic rats (Feng et al 2014), but the potential mechanisms remain to be fully elucidated.…”