title: Berberine moderates glucose metabolism through the GnRH-GLP-1 and MAPK pathways in the intestine.
abstract: BACKGROUND
  Berberine is known to improve glucose and lipid metabolism disorders, but it poorly absorbed into the blood stream from the gut. Therefore, the exact underlying mechanism for berberine is still unknown. In this study, we investigated the effect of berberine on glucose metabolism in diabetic rats and tested the hypothesis that berberine acts directly in the terminal ileums.
  
  
  METHODS
  Rats were divided into a control group, diabetic group (DM), low dose of berberine group (BerL) and high dose of berberine group (BerH). Ileum samples were analyzed using a Roche NimbleGen mRNA array, qPCR and immunohistochemistry.
  
  
  RESULTS
  We found that 8 weeks of treatment with berberine significantly decreased fasting blood glucose levels. An oral glucose tolerance test (OGTT) showed that blood glucose was significantly reduced in the BerL and BerH groups before and at 30 min, 60 min and 120 min after oral glucose administration. Plasma postprandial glucagon-like peptide-1 (GLP-1) levels were increased in the berberine-treated groups. The ileum from the BerH group had 2112 genes with significantly changed expression (780 increased, 1332 decreased). KEGG pathway analyses indicated that all differentially expressed genes included 9 KEGG pathways. The top two pathways were the MAPK signaling pathway and the GnRH signaling pathway. Q-RT-PCR and immunohistochemistry verified that glucagon-like peptide 1 receptor (Glp1r) and mitogen activated protein kinase 10 (Mapk10) were significantly up-regulated, in contrast, gonadotropin releasing hormone receptor (Gnrhr) and gonadotropin-releasing hormone 1 (Gnrh1) were down-regulated in the BerH group.
  
  
  CONCLUSIONS
  Our data suggest that berberine can improve blood glucose levels in diabetic rats. The mechanisms involved may be in the MAPK and GnRh-Glp-1 pathways in the ileum.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. xiaoxinhua@medmail.com.cn.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xiao
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Huabing
authors.initials: H
authors.lastname: Zhang
authors.forename: Fan
authors.initials: F
authors.lastname: Ping
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D050260:Carbohydrate Metabolism / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D015870:Gene Expression / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011498:Protein Precursors / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010936:Plant Extracts; D011498:Protein Precursors; D018027:Receptors, Glucagon; C050866:progonadoliberin I; D001599:Berberine; D007987:Gonadotropin-Releasing Hormone; D052216:Glucagon-Like Peptide 1; D005947:Glucose