Although administration of galanin or insulin alone may enhance insulin sensitivity and glucose transporter 4 (GLUT4) trafficking, their cooperative effect on insulin sensitivity is still unclear. In the present study, we evaluated the cooperative effect of both reagents compared with solitary treatment with galanin or insulin in type 2 diabetic rats. Galanin and/or insulin were injected singly or together into type 2 diabetic rats once a day for 15 days. The results indicated that coadministration of both reagents compared with treatment with galanin or insulin alone significantly increased glucose infusion rates in euglycemic–hyperinsulinemic clamp tests, 2-deoxy-[3H]d-glucose contents, GLUT4 densities, and pAS160 and protein kinase C activity levels, but reduced blood glucose and insulin levels, as well as retinol-binding protein 4 contents, and did not affect Glut4 (Slc2a4) mRNA expression levels in myocytes. The changes in the ratios of GLUT4 immunoreaction in plasma membranes to total cell membranes of myocytes were higher in the coadministrative group compared with either the insulin or the galanin group. These results indicate that cooperation of the two hormones plays a synergic role to improve GLUT4 translocation and insulin sensitivity. This finding indicates the possibility of combining galanin with insulin with the aim of obtaining better antidiabetic efficacy than that of the canonical treatment with insulin alone.
Le Bu, Qian Yao, Zhimin Liu, Wei Tang, Junjie Zou and Shen Qu
Lili Men, Junjie Yao, Shanshan Yu, Yu Li, Siyuan Cui, Shi Jin, Guixin Zhang, Decheng Ren and Jianling Du
The induction of endoplasmic reticulum (ER) stress is associated with adipogenesis, during which the inositol-requiring enzyme 1 alpha (IRE1α)-X-box-binding protein 1 (XBP1) pathway is involved. Selenoprotein S (SelS), which is an ER resident selenoprotein, is involved in ER homeostasis regulation; however, little is known about the role of SelS in regulating adipogenesis. In vivo studies showed that SelS protein levels in white adipose tissue were increased in obese subjects and high-fat diet (HFD)-fed mice. Moreover, we identified that SelS protein levels increased in the early phase of adipogenesis and then decreased in the late phase during adipogenesis. Overexpression of SelS promoted adipogenesis. Conversely, knockdown (KD) of SelS resulted in the inhibition of adipogenesis, which was related to increasing cell death, decreased mitotic clonal expansion, and cell cycle G1 arrest. In vivo studies also showed that ER stress markers (p-IRE1α/IRE1α, XBP1s, and Grp78) were significantly increased with upregulating of SelS expression in subcutaneous and visceral adipose tissues in the obese subjects and HFD-fed mice. Furthermore, in SelS KD cells, the levels of Grp78 were increased and the levels of p-IRE1α/IRE1α were unchanged , but mRNA levels of spliced XBP1 (XBP1s) produced by IRE1α-mediated splicing were decreased, suggesting a role of SelS in the modulation of IRE1α-XBP1 pathway. Moreover, inhibition of adipogenesis by SelS suppression can be rescued by overexpression of XBP1s. Thus, SelS appears to function as a novel regulator of adipogenesis through the IRE1α-XBP1 signaling pathway.