title: Direct activation of the proposed anti-diabetic receptor, GPR119 in cardiomyoblasts decreases markers of muscle metabolic activity.
abstract: GPR119 agonists are emerging rapidly as a pharmaceutical treatment of diabetes. Diabetes is a known risk factor for cardiovascular disease yet the cardiac-specific consequences of GPR119 activation are unknown. This study demonstrated that GPR119 agonism in cardiac myoblasts reduces metabolic activity in high and low concentrations of fatty acids, with high concentrations of palmitate largely attenuating the effects of the GPR119 agonist, PSN632408. The effects of GPR119 activation on gene and protein markers of metabolism were dependent on fatty acid exposure. Activating GPR119 did not affect cell hypertrophy of lipid accumulation regardless of lipid exposure. These results suggest that the pathways activated in response to GPR119 modulation in cardiac muscle cells differ between healthy and metabolically dysregulated states. However regardless of the pathway activated by GPR119, these effects may cause detrimental reductions to oxidative/metabolic capacity under both conditions. Thus further development of GPR119 agonists for treating metabolic diseases is warranted.
authors.affiliation: Centre for Chronic Disease Prevention and Management, College of Health and Biomedicine, Victoria University, Melbourne 8001, Australia.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Cornall
authors.affiliation: Department of Physiology, The University of Melbourne, Parkville 3000, Australia.
authors.forename: Deanne H
authors.initials: DH
authors.lastname: Hryciw
authors.affiliation: Centre for Chronic Disease Prevention and Management, College of Health and Biomedicine, Victoria University, Melbourne 8001, Australia.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Mathai
authors.affiliation: Centre for Chronic Disease Prevention and Management, College of Health and Biomedicine, Victoria University, Melbourne 8001, Australia. Electronic address: andrew.mcainch@vu.edu.au.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McAinch
mesh_terms: D000147:Acids, Heterocyclic / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D015536:Down-Regulation; D004734:Energy Metabolism; D015870:Gene Expression; D006801:Humans; D050356:Lipid Metabolism; D020935:MAP Kinase Signaling System; D032386:Myoblasts, Cardiac / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology*; D019308:Palmitic Acid / Q000494:pharmacology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*
chemical_list: D000147:Acids, Heterocyclic; D015415:Biomarkers; C532423:GPR119 protein, rat; D010069:Oxadiazoles; C534146:PSN 632408; D043562:Receptors, G-Protein-Coupled; D019308:Palmitic Acid; D000255:Adenosine Triphosphate
keywords: Cardiovascular disease; Diabetes; Fatty acids; GPR119