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Horm Metab Res 2013; 45(09): 646-651
DOI: 10.1055/s-0033-1343472
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Glucagon-like Peptide-1 Upregulates Visfatin Expression in 3T3-L1 Adipocytes

R. Liu
1   Department of Endocrinology, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, China
,
X. Ding
1   Department of Endocrinology, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, China
,
Y. Wang
1   Department of Endocrinology, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, China
,
M. Wang
1   Department of Endocrinology, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, China
,
Y. Peng
1   Department of Endocrinology, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, China
› Author Affiliations
Further Information

Publication History

received 14 December 2012

accepted 02 April 2013

Publication Date:
13 May 2013 (online)

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Abstract

The incretin hormone glucagon-like peptide-1 (GLP-1) exerts important functions in controlling glucose homeostasis. Many studies have revealed molecular targets of GLP-1, but its influence on adipokines has not been determined. Visfatin, a recently discovered adipokine, has been shown to attenuate insulin resistance by binding to insulin receptor. Our study shows that GLP-1 induced secretion of visfatin into the culture medium of 3T3-L1 adipocytes due to increased visfatin mRNA expression. Furthermore, the effect of GLP-1 on visfatin was dose- and time-dependent. H89, a protein kinase A inhibitor, prevented the induction of visfatin expression by GLP-1. Moreover, inhibition of NF-κB by PDTC reduced the basal visfatin release while having no effect on the transcription regulation by GLP-1. In addition, GLP-1 alleviated the decrease of visfatin mRNA expression under endoplasmic reticulum stress induced by thapsigargin. Taken together, our study suggests that GLP-1 promotes the novel insulin-mimetic adipocytokine visfatin expression via the PKA pathway and might influence glucose metabolism.

Key words

GLP-1 - visfatin - adipocyte - diabetes
 

  • References

  • 1 Todd JF, Wilding JP, Edwards CM, Khan FA, Ghatei MA, Bloom SR. Glucagon-like peptide-1 (GLP-1): a trial of treatment in non-insulin-dependent diabetes mellitus. Eur J Clin Invest 1997; 27: 533-536
    CrossrefPubMedGoogle Scholar
  • 2 Wang Q, Brubaker PL. Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice. Diabetologia 2002; 45: 1263-1273
    CrossrefPubMedGoogle Scholar
  • 3 Perfetti R, Zhou J, Doyle ME, Egan JM. Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, glucose-intolerant rats. Endocrinology 2000; 141: 4600-4605
    CrossrefPubMedGoogle Scholar
  • 4 Li Y, Hansotia T, Yusta B, Ris F, Halban PA, Drucker DJ. Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. J Biol Chem 2003; 278: 471-478
    CrossrefPubMedGoogle Scholar
  • 5 Patti ME, McMahon G, Mun EC, Bitton A, Holst JJ, Goldsmith J, Hanto DW, Callery M, Arky R, Nose V, Bonner-Weir S, Goldfine AB. Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy: evidence for inappropriate insulin secretion and pancreatic islet hyperplasia. Diabetologia 2005; 48: 2236-2240
    CrossrefPubMedGoogle Scholar
  • 6 Idris I, Patiag D, Gray S, Donnelly R. Exendin-4 increases insulin sensitivity via a PI-3-kinase-dependent mechanism: contrasting effects of GLP-1. Biochem Pharmacol 2002; 63: 993-996
    CrossrefPubMedGoogle Scholar
  • 7 Gao H, Wang X, Zhang Z, Yang Y, Yang J, Li X, Ning G. GLP-1 amplifies insulin signaling by up-regulation of IRbeta, IRS-1 and Glut4 in 3T3-L1 adipocytes. Endocrine 2007; 32: 90-95
    CrossrefPubMedGoogle Scholar
  • 8 Scrocchi LA, Brown TJ, MaClusky N, Brubaker PL, Auerbach AB, Joyner AL, Drucker DJ. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med 1996; 2: 1254-1258
    CrossrefPubMedGoogle Scholar
  • 9 Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab 1995; 80: 952-957
    CrossrefPubMedGoogle Scholar
  • 10 Buse JB, Drucker DJ, Taylor KL, Kim T, Walsh B, Hu H, Wilhelm K, Trautmann M, Shen LZ, Porter LE. DURATION-1 Study Group . Exenatide Once Weekly Produces Sustained Glycemic Control and Weight Loss Over 52 Weeks. Diabetes Care 2010; 33: 1255-1261
    CrossrefPubMedGoogle Scholar
  • 11 Vilsboll T, Zdravkovic M, Lethi T, Krarup T, Schmitz O, Courreges JP, Verhoeven R, Buganova I, Madsbad S. Liraglutide, a long-acting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care 2007; 30: 1608-1610
    CrossrefPubMedGoogle Scholar
  • 12 Liu R, Li Y, Hu R, Jin T, Deng S, Liang W, Zhang N, Chen J, Prud’homme GJ, Jia WW, Ma D, Wang Q. A site-specific genomic integration strategy for sustained expression of glucagon-like peptide-1 in mouse muscle for controlling energy homeostasis. Biochem Biophys Res Commun 2010; 403: 172-177
    CrossrefPubMedGoogle Scholar
  • 13 Parsons GB, Souza DW, Wu H, Yu D, Wadsworth SG, Gregory RJ, Armentano D. Ectopic expression of glucagon-like peptide 1 for gene therapy of type II diabetes. Gene Ther 2007; 14: 38-48
    CrossrefPubMedGoogle Scholar
  • 14 Lee YS, Shin S, Shigihara T, Hahm E, Liu MJ, Han J, Yoon JW, Jun HS. Glucagon-like peptide-1 gene therapy in obese diabetic mice results in long-term cure of diabetes by improving insulin sensitivity and reducing hepatic gluconeogenesis. Diabetes 2007; 56: 1671-1679
    CrossrefPubMedGoogle Scholar
  • 15 Oh S, Lee M, Ko KS, Choi S, Kim SW. GLP-1 gene delivery for the treatment of type 2 diabetes. Mol Ther 2003; 7: 478-483
    CrossrefPubMedGoogle Scholar
  • 16 Riedel MJ, Gaddy DF, Asadi A, Robbins PD, Kieffer TJ. DsAAV8-mediated expression of glucagon-like peptide-1 in pancreatic beta-cells ameliorates streptozotocin-induced diabetes. Gene Ther 2010; 17: 171-180
    CrossrefPubMedGoogle Scholar
  • 17 Xie H, Tang SY, Luo XH, Huang J, Cui RR, Yuan LQ, Zhou HD, Wu XP, Liao EY. Insulin-like effects of visfatin on human osteoblasts. Calcif Tissue Int 2007; 80: 201-210
    CrossrefPubMedGoogle Scholar
  • 18 Brown JE, Onyango DJ, Ramanjaneya M, Conner AC, Patel ST, Dunmore SJ, Randeva HS. Visfatin regulates insulin secretion, insulin receptor signalling and mRNA expression of diabetes-related genes in mouse pancreatic beta-cells. J Mol Endocrinol 2010; 44: 171-178
    CrossrefPubMedGoogle Scholar
  • 19 Skop V, Kontrová K, Zídek V, Pravenec M, Kazdová L, Mikulík K, Sajdok J, Zídková J. Autocrine effects of visfatin on hepatocyte sensitivity to insulin action. Physiol Res 2010; 59: 615-618
    PubMedGoogle Scholar
  • 20 Revollo JR, Korner A, Mills KF, Satoh A, Wang T, Garten A, Dasgupta B, Sasaki Y, Wolberger C, Townsend RR, Milbrandt J, Kiess W, Imai S. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab 2007; 6: 363-375
    CrossrefPubMedGoogle Scholar
  • 21 Cheng Q, Dong W, Qian L, Wu J, Peng Y. Visfatin inhibits apoptosis of pancreatic beta-cell line, MIN6, via the mitogen-activated protein kinase/phosphoinositide 3-kinase pathway. J Mol Endocrinol 2011; 47: 13-21
    CrossrefPubMedGoogle Scholar
  • 22 Sethi JK, Vidal-Puig A. Visfatin: the missing link between intra-abdominal obesity and diabetes?. Trends Mol Med 2005; 11: 344-347
    CrossrefPubMedGoogle Scholar
  • 23 Kim Chung LT, Hosaka T, Yoshida M, Harada N, Sakaue H, Sakai T, Nakaya Y. Exendin-4, a GLP-1 receptor agonist, directly induces adiponectin expression through protein kinase A pathway and prevents inflammatory adipokine expression. Biochem Biophys Res Commun 2009; 390: 613-618
    CrossrefPubMedGoogle Scholar
  • 24 Kendal CE, Bryant-Greenwood GD. Pre-B-cell colony-enhancing factor (PBEF/Visfatin) gene expression is modulated by NF-kappaB and AP-1 in human amniotic epithelial cells. Placenta 2007; 28: 305-314
    CrossrefPubMedGoogle Scholar
  • 25 Kim SR, Park HJ, Bae YH, Ahn SC, Wee HJ, Yun I, Jang HO, Bae MK, Bae SK. Curcumin down-regulates visfatin expression and inhibits breast cancer cell invasion. Endocrinology 2012; 153: 554-563
    CrossrefPubMedGoogle Scholar
  • 26 Yusta B, Baggio LL, Estall JL, Koehler JA, Holland DP, Li H, Pipeleers D, Ling Z, Drucker DJ. GLP-1 receptor activation improves beta cell function and survival following induction of endoplasmic reticulum stress. Cell Metab 2006; 4: 391-406
    CrossrefPubMedGoogle Scholar
  • 27 Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, Paschke R. Insulin resistance-inducing cytokines differentially regulate SOCS mRNA expression via growth factor- and Jak/Stat-signaling pathways in 3T3-L1 adipocytes. J Endocrinol 2004; 181: 129-138
    CrossrefPubMedGoogle Scholar
  • 28 Ognjanovic S, Bao S, Yamamoto SY, Garibay-Tupas J, Samal B, Bryant-Greenwood GD. Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes. J Mol Endocrinol 2001; 26: 107-117
    CrossrefPubMedGoogle Scholar
  • 29 Bala M, Martin J, Kopp A, Hanses F, Buechler C, Schaffler A. In vivo suppression of visfatin by oral glucose uptake: evidence for a novel incretin-like effect by glucagon-like peptide-1 (GLP-1). J Clin Endocrinol Metab 2011; 96: 2493-2501
    CrossrefPubMedGoogle Scholar
  • 30 Brubaker PL, Drucker DJ. Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors. Receptors Channels 2002; 8: 179-188
    CrossrefPubMedGoogle Scholar
  • 31 Sanz C, Vázquez P, Blázquez C, Barrio PA, Alvarez Mdel M, Blázquez E. Signaling and biological effects of glucagon-like peptide 1 on the differentiation of mesenchymal stem cells from human bone marrow. Am J Physiol Endocrinol Metab 2010; 298: E634-E643
    CrossrefPubMedGoogle Scholar
  • 32 Challa TD, Beaton N, Arnold M, Rudofsky G, Langhans W, Wolfrum C. Regulation of adipocyte formation by GLP-1/GLP-1R signaling. J Biol Chem 2012; 287: 6421-6430
    CrossrefPubMedGoogle Scholar
  • 33 Zhang X, Odom DT, Koo SH, Conkright MD, Canettieri G, Best J, Chen H, Jenner R, Herbolsheimer E, Jacobsen E, Kadam S, Ecker JR, Emerson B, Hogenesch JB, Unterman T, Young RA, Montminy M. Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci 2005; 102: 4459-4464
    CrossrefPubMedGoogle Scholar
  • 34 Kharroubi I, Ladriere L, Cardozo AK, Dogusan Z, Cnop M, Eizirik DL. Free fatty acids and cytokines induce pancreatic beta-cell apoptosis by different mechanisms: role of nuclear factor-kappaB and endoplasmic reticulum stress. Endocrinology 2004; 145: 5087-5096
    CrossrefPubMedGoogle Scholar
  • 35 Oyadomari S, Takeda K, Takiguchi M, Gotoh T, Matsumoto M, Wada I, Akira S, Araki E, Mori M. Nitric oxide-induced apoptosis in pancreatic beta cells is mediated by the endoplasmic reticulum stress pathway. Proc Natl Acad Sci USA 2001; 98: 10845-10850
    CrossrefPubMedGoogle Scholar
  • 36 Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH, Hotamisligil GS. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 2004; 306: 457-461
    CrossrefPubMedGoogle Scholar
  • 37 Pahl HL, Baeuerle PA. Expression of influenza virus hemagglutinin activates transcription factor NF-kappa B. J Virol 1995; 69: 1480-1484
    PubMedGoogle Scholar