title: Effect of Silymarin in Pdx-1 expression and the proliferation of pancreatic β-cells in a pancreatectomy model.
abstract: In type 1 Diabetes Mellitus (DM) there is a destruction of pancreatic β-cells (80-90%) at the time of detection, in DM type 2 these cells are decreased significantly. The Pdx1 transcription factor plays a central role in pancreatic development and in insulin gene expression. Previously, we have demonstrated that Silymarin recovers the normal morphology and endocrine function of damaged pancreatic tissue in alloxan induced diabetic rats. The aim of this study was to analyze the effect of Silymarin in Pdx1 gene expression and its repercussion on insulin gene expression and β-cell proliferation. 72 Wistar rats were partially pancreatectomized (60%) and divided into 12 groups. Six groups were treated daily with Silymarin (200mg/kg p.o.) for 3, 7, 14, 21, 42 and 63 day periods. Also, an unpancreatectomized control group was performed. At each time interval three animals from each group were administered BrdU 18 h before the sacrifice. Insulin and Pdx-1 gene expression were assessed by RT-PCR assay in total pancreatic RNA. β-Cell proliferation was determined by immunoperoxidase assay. In contrast to the animals that were only pancreatectomized, the Silymarin treatment induced an increase in both Pdx1 and insulin gene expression as well as β-cell proliferation in pancreatic tissue (control=2.6±0.28%; untreated=14.25±0.56%; treated=39.08±4.62%). Consequently, serum insulin levels rose (control=1.01±0.02 ng/ml; untreated=1.18±0.42 ng/ml; treated=4.58±0.58 ng/ml) and serum glucose levels decreased in these animals (control=6.2±0.01 mM; untreated=9.02±0.41 mM; treated=6.41±0.32 mM). These results suggest that Silymarin may induce the proliferation of insulin-producing cells.
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Mexico. Electronic address: casoto@correo.xoc.uam.mx.
authors.forename: C
authors.initials: C
authors.lastname: Soto
authors.affiliation: Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., Mexico.
authors.forename: L
authors.initials: L
authors.lastname: Raya
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Juárez
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Pérez
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Mexico.
authors.forename: I
authors.initials: I
authors.lastname: González
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020944:Silybum marianum / Q000737:chemistry*; D010180:Pancreatectomy; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D012313:RNA / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology* / Q000627:therapeutic use; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D010936:Plant Extracts; D012838:Silymarin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D012313:RNA
keywords: Insulin; Pancreatic regeneration; Pancreatic transcription factors; Silymarin