Probucol preserves pancreatic beta-cell function through reduction of oxidative stress in type 2 diabetes

Diabetes Res Clin Pract. 2002 Jul;57(1):1-10. doi: 10.1016/s0168-8227(02)00005-0.

Abstract

Oxidative stress is induced under diabetic conditions and causes various forms of tissue damage in patients with diabetes. Recently, pancreatic beta-cells have emerged as a putative target of oxidative stress-induced tissue damage and this seems to explain in part the progressive deterioration of beta-cell function in type 2 diabetes. As a step toward clinical trial of antioxidant for type 2 diabetes, we investigated the possible anti-diabetic effects of probucol, an antioxidant widely used as an anti-hyperlipidemic agent, on preservation of beta-cell function in diabetic C57BL/KsJ-db/db mice. Probucol-containing diet was given to mice from 6 to 16 weeks of age. Immunostaining for oxidative stress markers such as 4-hydroxy-2-nonenal (HNE)-modified proteins and heme oxygenase-1 revealed that probucol treatment decreased reactive oxygen species (ROS) in pancreatic islets of diabetic animals. Oxidative stress is known to enhance apoptosis of beta-cells and to suppress insulin biosynthesis, but probucol treatment led to preservation of beta-cell mass and the insulin content. According to intraperitoneal glucose tolerance tests, the probucol treatment preserved glucose-stimulated insulin secretion and improved glucose tolerance at 10 and 16 weeks: insulin, 280+/-82 vs. 914+/-238 pmol/l (120 min, at 16 weeks; P<0.05); glucose, 44.6+/-2.4 vs. 35.2+/-2.6 mmol/l (120 min, at 16 weeks; P<0.05). Thus, our present observations demonstrate the potential usefulness of probucol for treatment of type 2 diabetes.

MeSH terms

  • Animals
  • Antioxidants / therapeutic use*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Injections, Intraperitoneal
  • Insulin / administration & dosage
  • Insulin / blood
  • Insulin / metabolism
  • Insulin / pharmacology
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / pathology
  • Islets of Langerhans / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects*
  • Probucol / therapeutic use*

Substances

  • Antioxidants
  • Blood Glucose
  • Insulin
  • Probucol