title: Biliverdin protects against the deterioration of glucose tolerance in db/db mice.
abstract: OBJECTIVE
  We have previously shown a negative correlation between serum bilirubin levels and prevalence of type 2 diabetes, suggesting that bilirubin inhibits development of this disease. To confirm this hypothesis, we investigated whether administration of biliverdin, the precursor of bilirubin, protects against the deterioration of glucose tolerance in db/db mice, a rodent model of type 2 diabetes.
  
  
  METHODS
  Biliverdin (20 mg/kg daily) was orally administered to 5-week-old db/db mice for 4 weeks. After 4 weeks of treatment, i.p. glucose tolerance and insulin tolerance tests were performed. Insulin content was evaluated by immunostaining and ELISA. Oxidative stress markers (8-hydroxy-2'-deoxyguansosine and dihydroethidium staining) and expression of NADPH oxidase components Pdx1 and Bax were also evaluated in isolated islets.
  
  
  RESULTS
  Treatment with biliverdin partially prevented worsening of hyperglycaemia and glucose intolerance in db/db mice. This effect was accompanied by a significant increase in insulin content and Pdx1 expression, and a significant decrease of apoptosis and Bax expression in pancreatic islets from db/db mice. At the same time, levels of oxidative stress markers and NADPH oxidase component production in islets were normalised. Biliverdin had little effect on HOMA of insulin resistance or insulin resistance evaluated by insulin tolerance tests.
  
  
  CONCLUSIONS
  Biliverdin may protect against progressive worsening of glucose tolerance in db/db mice, mainly via inhibition of oxidative stress-induced beta cell damage.
authors: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: N
authors: N
authors: Ikeda
authors: T
authors: T
authors: Inoguchi
authors: N
authors: N
authors: Sonoda
authors: M
authors: M
authors: Fujii
authors: R
authors: R
authors: Takei
authors: E
authors: E
authors: Hirata
authors: H
authors: H
authors: Yokomizo
authors: J
authors: J
authors: Zheng
authors: Y
authors: Y
authors: Maeda
authors: K
authors: K
authors: Kobayashi
authors: R
authors: R
authors: Takayanagi
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