title: Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models.
abstract: BACKGROUND
  Catharanthus roseus (L). Don (Catharanthus roseus) is a traditional anti-diabetic herb widely used in many countries, and the alkaloids of Catharanthus roseus are considered to possess hypoglycemic ability.
  
  
  OBJECTIVE
  To systematically investigate the potential anti-diabetic effects and the underlying anti-diabetic mechanisms of vindoline, one of the alkaloids in Catharanthus roseus.
  
  
  METHODS
  The regulation of vindoline against the glucose-stimulated insulin secretion (GSIS) was examined in insulinoma MIN6 cells and primary pancreatic islets. Insulin concentration was detected by Elisa assay. Diabetic models of db/db mice and type 2 diabetic rats induced by high-fat diet combining with streptozotocin (STZ/HFD-induced type 2 diabetic rats) were used to evaluate the anti-diabetic effect of vindoline in vivo. Daily oral treatment with vindoline (20mg/kg) to diabetic mice/rats for 4 weeks, body weight and blood glucose were determined every week, oral glucose tolerance test (OGTT) was performed after 4 weeks.
  
  
  RESULTS
  Vindoline enhanced GSIS in both glucose- and dose-dependent manners (EC50 = 50 μM). It was determined that vindoline acted as a Kv2.1 inhibitor able to reduce the voltage-dependent outward potassium currents finally enhancing insulin secretion. It protected β-cells from the cytokines-induced apoptosis following its inhibitory role in Kv2.1. Moreover, vindoline (20mg/kg) treatment significantly improved glucose homeostasis in db/db mice and STZ/HFD-induced type 2 diabetic rats, as reflected by its functions in increasing plasma insulin concentration, protecting the pancreatic β-cells from damage, decreasing fasting blood glucose and glycated hemoglobin (HbA1c), improving OGTT and reducing plasma triglyceride (TG).
  
  
  CONCLUSIONS
  Our findings suggested that vindoline might contribute to the anti-diabetic effects of Catharanthus roseus, and this natural product may find its more applications in the improvement of β-cell dysfunction and further the potential treatment of type 2 diabetes.
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Xin-gang
authors.initials: XG
authors.lastname: Yao
authors.forename: Fanglei
authors.initials: F
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Lingling
authors.initials: L
authors.lastname: Quan
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.forename: Chenjing
authors.initials: C
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.forename: Zhaobing
authors.initials: Z
authors.lastname: Gao
authors.forename: Ping
authors.initials: P
authors.lastname: Wan
authors.forename: Lihong
authors.initials: L
authors.lastname: Hu
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
mesh_terms: D000818:Animals; D029062:Apocynaceae; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003412:Cricetulus; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D057809:HEK293 Cells; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D026902:Potassium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D005947:Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D026902:Potassium Channel Blockers; D014747:Vinblastine; C009667:vindoline
keywords: Catharanthus roseus; Catharanthus roseus (L). Don; FSK; GSIS; Glucose-stimulated insulin secretion; Gly; HFD; HbA(1c); LAME; OGTT; STZ; TEA; TG; Type 2 diabetes; Vindoline; forskolin; glucose-stimulated insulin secretion; glybenclamide; glycated hemoglobin; high-fat diet; linoleic acid methyl ester.; oral glucose tolerance test; plasma triglyceride; streptozotocin; tetraethylammonium chloride; β-cell dysfunction