Probucol preserves pancreatic beta-cell function through reduction of oxidative stress in type 2 diabetes.
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.
Gorogawa
Shin ichi
Si
Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka Pref, Japan.
Kajimoto
Yoshitaka
Y
Umayahara
Yutaka
Y
Kaneto
Hideaki
H
Watada
Hirotaka
H
Kuroda
Akio
A
Kawamori
Dan
D
Yasuda
Tetsuyuki
T
Matsuhisa
Munehide
M
Yamasaki
Yoshimitsu
Y
Hori
Masatsugu
M
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D011341:Probucol / Q000627:therapeutic use*
D000975:Antioxidants; D001786:Blood Glucose; D007328:Insulin; D011341:Probucol