Biliverdin protects against the deterioration of glucose tolerance in db/db mice

Diabetologia. 2011 Aug;54(8):2183-91. doi: 10.1007/s00125-011-2197-2. Epub 2011 May 26.


Aims/hypothesis: 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/interpretation: Biliverdin may protect against progressive worsening of glucose tolerance in db/db mice, mainly via inhibition of oxidative stress-induced beta cell damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biliverdine / therapeutic use*
  • Blood Glucose / drug effects
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucose Intolerance / drug therapy*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • In Vitro Techniques
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction


  • Blood Glucose
  • Biliverdine