Type 2 diabetes is manifested by progressive metabolic impairments especially in skeletal muscle which becomes resistant to insulin. From KO mouse phenotype analyses (http://www.mousephenotype.org), we identified that loss of function of Melanocortin 2 Receptor Accessory Protein 2 (Mrap2) could induce metabolic disorders through Prokineticin receptor 1 (Prokr1/Gpr73). In this study, we investigated the possible role of Prokr1 in myogenesis and insulin resistance using murine myoblast cell line (C2C12) and primary mouse muscular satellite cells. We examined the expression levels of Prokr1 in C2C12 and muscular satellite cells during myogenic differentiation, and Prokr1 was upregulated during myogenic differentiation at mRNA and protein levels. Prokineticin 2 (Pk2), a natural ligand of Prokr1, induced intracellular calcium mobilization and cAMP generation in dose-dependent manner. Activation of Prokr1 using Pk2 led to increase the number of myoblast and myotube formation. It also induced Akt1 phosphorylation throughout the myogenesis without insulin stimulation. In myotube, Prokr1 activation increased Slc2a4/Glut4 expression, resulted in 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake as well. Prokr1-mediated insulin resistance was attenuated in palmitate-induced insulin resistant myotube. These effects had been abolished in Prokr1 KO C2C12 cells. These results suggest that Prokr1 could be a crucial player in myogenesis and insulin resistance. Our data support the emerging concept that Prokr1 is a potential target for treatment of insulin resistance in type 2 diabetes mellitus.
M. Jongsoo: None. J. Park: None.
