title: Hyperglycemia- and hyperinsulinemia-induced alteration of adiponectin receptor expression and adiponectin effects in L6 myoblasts.
abstract: Adiponectin has been shown to regulate glucose and fatty acid uptake and metabolism in skeletal muscle. Here we investigated the role of the recently cloned adiponectin receptor (AdipoR) isoforms in mediating effects of both globular (gAd) and full-length (fAd) adiponectin, and their regulation by hyperglycemia (25 mM, 20 h) and hyperinsulinemia (100 nM, 20 h). We used L6 rat skeletal muscle cells, which were found to express both AdipoR1 and AdipoR2 mRNA in a ratio of over 6:1 respectively. Hyperglycemia and hyperinsulinemia both decreased AdipoR1 receptor expression by approximately 50%, while the latter induced an increase of approximately threefold in AdipoR2 expression. The ability of gAd to increase GLUT4 myc translocation, glucose uptake, fatty acid uptake and oxidation, as well as AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, was decreased by both hyperglycemia and hyperinsulinemia. Interestingly, hyperinsulinemia induced the ability of fAd to elicit fatty acid uptake and enhanced fatty acid oxidation in response to fAd. In summary, our results suggest that both hyperglycemia and hyperinsulinemia cause gAd resistance in rat skeletal muscle cells. However, hyperinsulinemia induces a switch toward increased fAd sensitivity in these cells.
authors.affiliation: Department of Biology, York University, Toronto, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Fang
authors.forename: R
authors.initials: R
authors.lastname: Palanivel
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Sweeney
mesh_terms: D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D052242:Adiponectin / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006943:Hyperglycemia / Q000235:genetics* / Q000378:metabolism; D006946:Hyperinsulinism / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D018076:DNA, Complementary; D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D009097:Multienzyme Complexes; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495694:Slc2a4 protein, rat; C504339:adiponectin receptor 1, rat; C506573:adiponectin receptor 2, rat; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D005947:Glucose