Platelet-Derived Growth Factor Stimulates Glucose Transport in Skeletal Muscles of Transgenic Mice Specifically Expressing Platelet-Derived Growth Factor Receptor in the Muscle, but It Does Not Affect Blood Glucose Levels

Abstract

Insulin stimulates the disposal of blood glucose into skeletal muscle and adipose tissues by the translocation of GLUT4 from intracellular pools to the plasma membrane, and consequently the concentration of blood glucose levels decreases rapidly in vivo. Phosphatidylinositol (PI) 3-kinase and Akt play a pivotal role in the stimulation of glucose transport by insulin, but detailed mechanisms are unknown. We and others reported that not only insulin but also platelet-derived growth factor (PDGF) and epidermal growth factor facilitate glucose uptake through GLUT4 translocation by activation of PI 3-kinase and Akt in cultured cells. However, opposite results were also reported. We generated transgenic mice that specifically express the PDGF receptor in skeletal muscle. In these mice, PDGF stimulated glucose transport into skeletal muscle in vitro and in vivo. Thus, PDGF apparently shares with insulin some of the signaling molecules needed for the stimulation of glucose transport. The degree of glucose uptake in vivo reached ϳ60% of that by insulin injection in skeletal muscle, but blood glucose levels were not decreased by PDGF in these mice. Therefore, PDGF-induced disposal of blood glucose into skeletal muscle is insufficient for rapid decrease of blood glucose levels. Diabetes

The Rab GTPase-Activating Protein AS160 Integrates Akt, Protein Kinase C, and AMP-Activated Protein Kinase Signals Regulating GLUT4 Traffic

“…AS160 relays insulin and PDGF signaling to GLUT4. PDGF stands out due to its ability to activate Akt and GLUT4 translocation in cells that coexpress PDGF receptors and GLUT4 (12,13,41). Before the current research was undertaken, it was not known whether Akt is requisite to achieving GLUT4 externalization by PDGF.…”

“…In addition to insulin, platelet-derived growth factor (PDGF), which also increases Akt phosphorylation, stimulates GLUT4 exocytosis and glucose transport in cells with an endogenous PDGF receptor (12) or through ectopic expression (13). Also, exercise/contraction, K ϩ depolarization (14), or a rise in intracellular Ca 2ϩ levels (15) all increase surface GLUT4 levels and glucose uptake in skeletal muscle and cultured muscle cells.…”

Beta Interferon Regulation of Glucose Metabolism Is PI3K/Akt Dependent and Important for Antiviral Activity against Coxsackievirus B3

“…A number of studies have confirmed the roles of PI3K and Akt signaling in regulating glucose uptake induced by growth factors or cytokines in adipocytes, skeletal muscle cells, and lymphocytes (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Our strategy was to examine the contribution of different effector intermediates in the PI3K/Akt/mTOR signaling cascade to the IFN-␤-inducible regulation of glucose uptake that we observed, specifically, by using MEFs with targeted disruption of certain genes (Fig.…”

“…AMP-activated protein kinase (AMPK), an important sensor of cellular ATP flux, is invoked to balance energy-consuming pathways, mediated by regulation of mTOR and glucose uptake (23). Indeed, various growth factors (insulin, platelet-derived growth factor [PDGF], insulinlike growth factor 1 [IGF-1], and vascular endothelial growth factor [VEGF]) and cytokines (interleukin-3 [IL-3], IL-5, IL-6, IL-7, granulocyte-macrophage colony-stimulating factor [GM-CSF], tumor necrosis factor-alpha [TNF-␣], and CCL5) that signal through PI3K/Akt/mTOR have been shown to regulate glucose metabolism, specifically through the PI3K/Akt/mTOR pathway (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). Cognizant that IFN-␣/␤ engage PI3K/Akt/mTOR signal-The cell lysates were then diluted 10 times with 100 mM Tris, 2 mM EDTA, pH 7.75, and assayed for intracellular ATP using an ATP bioluminescent assay kit (Sigma).…”

The Rab GTPase-Activating Protein AS160 as a Common Regulator of Insulin- and G.ALPHA.q-Mediated Intracellular GLUT4 Vesicle Distribution

“…mouse monoclonal antibodies against β-tubulin (Tub 2.1) (T4026) were purchased from sigma (st. Louis, mi). mouse mono-3-K and akt as well as insulin, also facilitate gLuT4 translocation and glucose transport in cultured cells [3][4][5][6][7][8][9] and skeletal muscles of transgenic mice expressing the PDgF receptor [10]. moreover, it is also reported that atypical protein kinase c isoforms [11,12] and Tc10, a member of the rho family of small gTPases [13], are implicated in insulin-induced gLuT4 translocation.…”