title: Exendin-4 Upregulates Adiponectin Level in Adipocytes via Sirt1/Foxo-1 Signaling Pathway.
abstract: Glucagon-like peptide-1 (GLP-1) receptor plays an essential role in regulating glucose metabolism. GLP-1 receptor agonists have been widely used for treating diabetes and other insulin resistance-related diseases. However, mechanisms underlying the anti-diabetic effects of GLP-1 receptor agonists remain largely unknown. In this study, we investigated the effects of GLP-1 agonist exendin-4 on the expression of adiponectin, an insulin sensitizing hormone. We found that exendin-4 increased the expression and secretion of adiponectin both in vitro and in vivo. Our data showed that exendin-4 upregulated adiponectin expression at both mRNA and protein levels in adipocytes and adipose tissues. The effects of exendin-4 on adiponectin expression were dependent on the GLP-1 receptor. We further demonstrated important roles of Sirt1 and transcriptional factor Foxo-1 in mediating the function of exendin-4 in regulating adiponectin expression. Suppression of Sirt1 or Foxo-1 expression significantly impaired exendin-4-induced adiponectin expression. Consistently, exendin-4 up-regulated Sirt1 and Foxo-1 expression in vivo. Our work is the first study demonstrating the role of Sirt1/Foxo-1 in regulating the regulatory function of a GLP-1 receptor agonist in adiponectin expression both in vitro and in vivo. The results provide important information for the mechanism underlying the function of GLP-1R on improving insulin resistance and related diseases.
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Anping
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Baoan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Mu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000077270:Exenatide; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000235:genetics / Q000378:metabolism; D054795:Incretins / Q000494:pharmacology*; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; D000071161:Forkhead Box Protein O1; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D056564:Sirtuin 1