title: Role and mechanism of rosiglitazone on the impairment of insulin secretion induced by free fatty acids on isolated rat islets.
abstract: BACKGROUND
  Prolonged exposure of pancreatic beta-cells to fatty acids increases basal insulin secretion but inhibits glucose-stimulated insulin secretion. Rosiglitazone is a new antidiabetic agent of the thiazolidinediones. However, the relationship between thiazolidinediones and insulin secretion is highly controversial. The aim of this study is to explore the effect and mechanism of rosiglitazone on insulin secretion of islets under chronic exposure to free fatty acids (FFA).
  
  
  METHODS
  Pancreatic islets were isolated from the pancreata of male Sprague-Dawley rats by the collagenase digestion and by the dextran gradient centrifugation method. The purified islets were cultured in the presence or absence of rosiglitazone and palmitate for 48 hours. The insulin secretion was measured by radioimmunoassay. The mRNA level of peroxisome proliferator-activated receptor gamma, uncoupling protein 2 (UCP-2) and insulin were determined by real-time polymerase chain reaction (PCR). The cell cytotoxicity assay was measured by cell counting kit-8.
  
  
  RESULTS
  Islets exposed to elevated palmitate for 48 hours showed an increased basal and a decreased glucose-stimulated insulin secretion (P < 0.01). The mRNA level of UCP-2 was increased by 3.7 fold in the 0.5 mmol/L concentration of palmitate. When islets were cultured with palmitate (0.5 mmol/L) in the presence of rosiglitazone (1.0 micromol/L), both basal and glucose-stimulated insulin secretion reversed to a pattern of control islets (P < 0.05, P < 0.01). The addition of rosiglitazone in the culture medium decreased the mRNA level of UCP-2 by 2.2 fold, having a statistically significant difference (P < 0.05) as compared with islets cultured with palmitate alone. The cell viability was not affected.
  
  
  CONCLUSIONS
  The protective effects of rosiglitazone on insulin secretion of isolated pancreatic islets under chronic exposure to palmitate might be mediated through the downregulation of UCP-2 expression.
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
authors.forename: Jing-yan
authors.initials: JY
authors.lastname: Tian
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.forename: Yan-yun
authors.initials: YY
authors.lastname: Gu
authors.forename: Hong-li
authors.initials: HL
authors.lastname: Zhang
authors.forename: Wen-zhong
authors.initials: WZ
authors.lastname: Zhou
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Hong-da
authors.initials: HD
authors.lastname: Zhu
authors.forename: Tian-hong
authors.initials: TH
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Luo
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007473:Ion Channels; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D000071246:Uncoupling Protein 2
chemical_list: D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D000077154:Rosiglitazone