title: Regulation of glucose and lipid homeostasis by adiponectin: effects on hepatocytes, pancreatic β cells and adipocytes.
abstract: Adiponectin has received considerable attention for its potential anti-diabetic actions. The adipokine exerts control of glucose and lipid homeostasis via critical effects within the liver, adipose, and pancreas. By stimulating adipogenesis, opposing inflammation, and influencing rates of lipid oxidation and lipolysis, adiponectin critically governs lipid spillover into non-adipose tissues. Ceramide, a cytotoxic and insulin desensitizing lipid metabolite formed when peripheral tissues are exposed to excessive lipid deposition, is potently opposed by adiponectin. Via adiponectin receptors, AdipoR1 and AdipoR2, adiponectin stimulates the deacylation of ceramide- yielding sphingosine for conversion to sphingosine 1-phosphate (S1P) by sphingosine kinase. The resulting conversion from ceramide to S1P promotes survival of functional beta cell mass, allowing for insulin production to meet insulin demands. Alleviation of ceramide burden on the liver allows for improvements in hepatic insulin action. Here, we summarize how adiponectin-induced changes in these tissues lead to improvements in glucose metabolism, highlighting the sphingolipid signaling mechanisms linking adiponectin to each action. ONE SENTENCE SUMMARY: We review the anti-diabetic actions of adiponectin.
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Tao
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA.
authors.forename: Angelica
authors.initials: A
authors.lastname: Sifuentes
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA. Electronic address: william.holland@utsouthwestern.edu.
authors.forename: William L
authors.initials: WL
authors.lastname: Holland
mesh_terms: D017667:Adipocytes / Q000187:drug effects; D052242:Adiponectin / Q000502:physiology*; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002518:Ceramides / Q000096:biosynthesis; D015536:Down-Regulation; D005234:Fatty Liver / Q000517:prevention & control; D005947:Glucose / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008246:Lysophospholipids / Q000502:physiology; D051379:Mice; D013110:Sphingosine / Q000031:analogs & derivatives / Q000502:physiology; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D002518:Ceramides; D008246:Lysophospholipids; D053778:Thiazolidines; C060506:sphingosine 1-phosphate; D005947:Glucose; D013110:Sphingosine
keywords: ceramide; insulin resistance; obesity