eISSN:2278-5299

International Journal of Latest Research in Science and Technology

DOI:10.29111/ijlrst   ISRA Impact Factor:3.35,  Peer-reviewed, Open-access Journal

A News Letter Sign UP!
SILYMARIN INDUCES GLUCAGON LIKE PEPTIDE-1 SECRETION AND INCREASES ITS RECEPTOR GENE EXPRESSION IN PANCREATIC TISSUE IN PARTIALLY PANCREATECTOMIZED RATS

Research Paper Open Access

International Journal of Latest Research in Science and Technology Vol.6 Issue 3, pp 13-19,Year 2017

SILYMARIN INDUCES GLUCAGON LIKE PEPTIDE-1 SECRETION AND INCREASES ITS RECEPTOR GENE EXPRESSION IN PANCREATIC TISSUE IN PARTIALLY PANCREATECTOMIZED RATS

Claudia Soto, Imelda Gonz?lez, Luis Raya, Ulises Carrasco, Luz Tovar

Correspondence should be addressed to :

Received : 29 April 2017; Accepted : 20 May 2017 ; Published : 30 June 2017

Share
Download 125
View 180
Article No. 10725
Abstract

Glucagon-like peptide-1 (GLP-1) is an incretin produced and released by gut endocrine L-cells in response to the ingestion of carbohydrates, lipids and proteins. It is also produced in the pancreatic tissue, both in humans and rats. In the pancreatic tissue, GLP-1, stimulates insulin secretion in β-cells, induces neogenesis, proliferation, differentiation and maintenance of β cell mass, and inhibits apoptosis of these cells. For these reasons, this peptide has been used in the management of type 2 diabetes mellitus (DM) and has also been tried in type 1 DM. The action of GLP-1 on β cells is initiated through binding with a GLP-1 membrane bound receptor (GLP-1R), coupled to G protein, which leads to a rise in cyclic AMP (cAMP) and calcium levels, followed by insulin secretion. It was reported that GLP-1 induces an increase of PDX-1 gene expression levels and enhances the transcription of the insulin gene by increasing the binding of PDX-1 transcription factor to the insulin gene promotor region. We reported previously that silymarin induces both PDX-1 transcription factor and the insulin gene expression, as well as β-cell proliferation in pancreatic tissue. In this study we demonstrated that silymarin treatment to partially pancreatectomized rats increases pancreatic: GLP-1R gene expression, tissue immunoreactivity for GLP-1, densitometry of this peptide for Western blot analysis, proliferation of GLP-1 secreting cells, insulin serum concentration and a decrease in glucose serum. All these tests were performed to show the contrast with untreated pancreatectomized animals. Our results may suggest that silymarin increases the secretion of pancreatic GLP-1, and its activity. It would seem that it may be related to the increase in the PDX-1 transcription factor previously reported in silymarin treatment of partially pancreatectomized rats.

Key Words   
proliferation of pancreatic GLP-1 producing cells, GLP-1 pancreatic receptor, GLP-1R, GLP-1 pancreat
Copyright
References
  1. Marathe C, Rayner C, Jones K, Horowitz M. Glucagon like peptides 1 and 2 in health an disease: A review. Peptides 2013;424:75-86.
  2. Uttenthal L, Ghiglione M, George S, Bisho E, Polak J, Bloom S. Molecular forms of glucagon-like peptide-1 in human pancreas and glucagonomas. J Clin Endocrinol Metab 1985;61:472-479.
  3. Varndell I, Bishop A, Sikri K, Uttenthal L, Bloom S, Polack J. Localization of glucagon-like peptide (GLP) immunoreactants in human gut and pancreas using light and electron microscopic immunocytochemistry. J Histochem Cytochem 1985;33:1080-1086.
  4. Mojsov S, Kopezynski M, Habener J. Both amidated and nonmidates forms of glucagon-like peptide 1 are synthesized in the rat intestine and the pancreas. J Biol Chem 1990;265:8001-8008.
  5. Marchetti P, Lupi R, Bugliani M, Kirkpatrick C, Sebastian G, Grieco F, Del Guerra S, D' Aleo V, Piro S, Marselli L, Bogg U, Filipponi F, Tinti L, Salvani, Woolheim C, Purrello F, Dotta F. A local glucagón-like peptide 1 (GLP-1) system in human pancreatic islets. Diabetologia 2012;55:3262-3272.
  6. Fehmann HC, Göke R, Göke B. Cell and molecular biology of the incretin hormones glucagon-like peptide-I and glucose-dependent insulin releasing polypeptide.Endocr Rev 1995;16:390–410
  7. Zhang F, Tang X, Cao H, Lü Q, Li N, Liu Y, Zhang X, Zhang Y, Cao M, Wan Y, An Z, Tong N.. Impaired Secretion of Total Glucagon-like Peptide-1 in People with Impaired Fasting Glucose Combined Impaired Glucose Tolerance. Int Jour Med Sci 2012;9:574-581
  8. Mojsov S, Weir, G, Habener J. Insulinotropin: glucagon-like peptide 1 (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat páncreas.. J Clin Invest 1987;79:616-619.
  9. Drucker D. Glucagon like peptides: regulators of cell proliferation, differentiation and apoptosis. Mol Endocrinol 2003;17:161-171.
  10. Buteau J. GLP-1 receptor signaling: effects on pancreatic cell proliferation and survival. Diab. Metab 2008;34(Supl 2):S73-77.
  11. Rondas D, D' Hertog L, Overbergh L, Mathieu C. Glucagon-like peptide-1: modulator of β-cell dysfunction and death. Diabetes, Obesity and Metabolism 2013;15 (Suppl.3):185-192.
  12. Girard J. The incretins: From the concept to their use in the treatment of type 2 diabetes. Part A: Incretins concept and physiological function. Diab Metab 2008;34:550-559.
  13. Kielgast U, Holst J, Madsbad S. Antidiabetic actions of exogenous and endogenous GLP-1 in type 1 patients with and without residual beta-cell function. Diabetes 2011;60:1599-607.
  14. Drucker D, Philippe J, Mojsov S, Chick W, Habener J. Glucagon-like peptide 1 stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci USA 1987;84:3434-3438.
  15. Thorens B. Expression and cloning of the pancreatic beta cell receptor for the gluco-incretin hormone glucagon-like peptide 1. Proc Natl Acad Sci USA, 1992;89:8641-8645.
  16. Kang G, Leech C, Chepumy O, Coetzee W, Holz G. Role of the cAMP sensor Epac as a determinant of K-ATP channel ATP sensivity in human pancreatic beta cells and rat INS-1 cells. J Physiol 2008;586:1307-1319.
  17. Gromada J, Bokvist K, Ding W, Holst J, Nielsen J, Rorsman P. Glucagon-like peptide 1 (7-36) amide stimulates exocytosis in human pancreatic beta-cells by both proximal and distal regulatory steps in stimulus-secretion coupling. Diabetes 1998;47:57-65.
  18. Wang J, Egan M, Raigad O, Nadiv J, Roth C, Montrose R. Glucagon-like peptide-1 affects gene transcription and messenger ribonucleic acid stability of components of the insulin secretory system in RIN1046-38 cells. Endocrinology 1995;136:4910-4917.
  19. Wang X, Cahill C, Pineyro M, Zhou J, Doyle M, Egan J. Glucagon-like peptide-1 regulates the beta cell transcription factor PDX-1 in insulinoma cells. Endocrinology 1999;140:4904-4970.
  20. Perfetti R, Zhou J, Doyle M, Egan J. Glucagon-like peptide-1 induces cell proliferation and pancreatic-duoden homeobox-1 expression and increases endocrine cell mass in the pancreas of old glucose-intolerant rats. Endocrinology 2000;141:4600-4605.
  21. Stoffers D, Kieffer T, Hussain M, Drucker D, Bonner-Weir S, Habener J, Egan J. Insulinotropic glucagon-like peptide-1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. Diabetes 2000;49:741-748.
  22. Chakrabarti S, James J, Mirmira R. Quantitative assessment of genetargetingin vitro and in vivo by the pancreatic transcription factor, Pdx 1. Importance of chromatin structure in directing promoter binding. J Biol Chem 2000;277:13286–13293.
  23. Dalle S, Quoyer J, Varin E, Costes S. Roles and regulation of the transcription factor CREB in pancreatic beta-cells. Curr Mol Pharmacol 2011;4:187-195.
  24. Soto C, Raya L, Juárez J. Pérez J, González I. Effect of Silymarin in Pdx-1 expression and the proliferation of pancreatic β-cells in a pancreatectomy model. Phytomedicine 2014;21:233-239.
  25. Abenavoli L, Caspasso R, Milic N, Caspasso F. Milk thistle in liver diseases: past, present, future. Phytother Res 2010;24:1423-1432.
  26. Lotfy M, Singh J, Rashed H, Tariq S, Zilahi, Adeghate E. The effect of glucagon-like peptide-1 in the management of diabetes mellitus: cellular and molecular mechanisms. Cell Tissue Research 2014;358:343-358.
  27. Vetter M, Cardillo S, Rickels M, Iqbal N. Narrative review: effect of bariatric surgery on type 2 diabetes mellitus. Ann Intern Med 2009;150:94-103.
  28. De León D, Deng S, Madani R, Ahima R, Drucker D, Stoffers D. Role of endogenous glucagón-like peptide-1 in islet regeneration after partial pancreatectomy. Diabetes 2003;52:365-371.
  29. Yazhou L, Hansotia T, Yusta B, Ris F, Halban P, Drucker D. Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. J Biol Chem 2003;278:471–478.
  30. Xu G, Stoffers D, Habener J, Bonner-Weir S. Exendin-4 stimulates both β-cell replication and neogenesis, resulting in increased β-cell mass and improved glucose tolerance in diabetic rats. Diabetes 1999;48:2270-2276.
  31. Wideman R, Yu I, Webber T, Verchere B, Johnson J. Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1). Proc Natl Acad Sci 2006;103:13468-13473.
  32. Babu D, Deering T, Mirmira R. A feat of metabolic proportions: Pdx1 orchestrates islet development and function in the maintenance of glucose homeostasis. Mol Genet Metab 2007;92:43-55.
  33. Campbell S, Macfarlane W. Regulation of the pdx1 gene promoter in pancreatic β-cells. Biochem Biophys Res Comm 2002;299:277-284.
  34. Wang Q, Li L, Xu E, Wong V, Rhodes C, Brubaker P. Glucagon-like peptide-1 regulates proliferation and apoptosis via activation of protein kinase B in pancreatic (INS-1) beta cells. Diabetologia 2004;47:478-487.
  35. Shiota C, Larsson O, Shelton K, Shiota M, Efanov A, Hoy M, Lindner J, Kooptiwut S, Juntti-Bergen L, Gromada J, Berggren P, Magnuson M. Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose. 2004. J Biol Chem 2002;277:37176-37183.
  36. Gauthier B, Brun T, Sarret E, Ishihara H, Schaad O, Descombes P, Wollheim C. Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets. J Biol Chem 2004;279:31121-31130.
  37. Iype T, Francis J, Garmey J, Schisler J, Nesher R, Weir G, Becker T, Newgard C, Griffen S, Mirmira R. Mechanism of insulin gen regulation by the pancreatic transcription factor Pdx-1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes. J Biol Chem 2005;280:16798-16807.  
  38. Yazhou L, Cao X, Li L, Brubaker P, Hedlund H, Drucker D. β-cell Pdx1 expression is essential for the regulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. Diabetes 2005;54:482-491.
  39. Soto C, Recoba R, Barrón H, Álvarez C, Favari L. Silymarin increases the pancreatic activity of antioxidant enzymes in alloxan-induced diabetes mellitus in the rat. Comp Biochem. Physio 2003;136C:205-212.
To cite this article

Claudia Soto, Imelda Gonz?lez, Luis Raya, Ulises Carrasco, Luz Tovar , " Silymarin Induces Glucagon Like Peptide-1 Secretion And Increases Its Receptor Gene Expression In Pancreatic Tissue In Partially Pancreatectomized Rats ", International Journal of Latest Research in Science and Technology . Vol. 6, Issue 3, pp 13-19 , 2017


Responsive image

MNK Publication was founded in 2012 to upholder revolutionary ideas that would advance the research and practice of business and management. Today, we comply with to advance fresh thinking in latest scientific fields where we think we can make a real difference and growth now also including medical and social care, education,management and engineering.

Responsive image

We offers several opportunities for partnership and tie-up with individual, corporate and organizational level. We are working on the open access platform. Editors, authors, readers, librarians and conference organizer can work together. We are giving open opportunities to all. Our team is always willing to work and collaborate to promote open access publication.

Responsive image

Our Journals provide one of the strongest International open access platform for research communities. Our conference proceeding services provide conference organizers a privileged platform for publishing extended conference papers as journal publications. It is deliberated to disseminate scientific research and to establish long term International collaborations and partnerships with academic communities and conference organizers.