title: Diversity in the utilization of glucose and lactate in synthetic mammalian myotubes generated by engineered configurations of MyoD and E12 in otherwise non-differentiation growth conditions.
abstract: We previously used the expression of various combinations and configurations of MyoD and E12, two basic helix-loop-helix transcription factors (TF), to produce populations of myotubes assuming distinct morphology, myofibrillar development and Ca2+ dynamics, from mammalian C2C12 myoblasts in non-differentiation growth conditions. Here, we assessed the synthetically generated myotubes in terms of energetics, otherwise necessary to sustain their mechanical output as bio-actuators. We found that the myotubes exhibit changed expression of key regulators for the uptake and utilization of two major cellular fuels, glucose and lactate. Furthermore, while lactate transport was uniformly slowed in all the populations of myotubes, glucose uptake and utilization were modified by particular TF configuration. Our approach allows the production of a class of biomaterials with predetermined energetics that could be applied in biorobotics, where fuel of choice could be used, and also in reparative medicine where, for example, particular population of myotubes could be additionally employed as glucose sinks to mitigate effects of secondary metabolic syndrome.
authors.affiliation: Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Grubišić
authors.affiliation: Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia. Electronic address: vlad@uab.edu.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Parpura
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D017570:MyoD Protein / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D058127:Transcription Factor 3 / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D051275:Glucose Transporter Type 4; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C495693:Slc2a4 protein, mouse; D058127:Transcription Factor 3; D019344:Lactic Acid; D005947:Glucose; D002118:Calcium
keywords: GLUT4; Glucose transporter 1 (GLUT1); Hexokinase 2 (HK2); MCT4; Monocarboxylate transporter 1 (MCT1)