Amelioration of the beta-cell
dysfunction in diabetic APA hamsters by antioxidants and AGE inhibitor
treatments.
Takatori A, Ishii Y, Itagaki S, Kyuwa
S, Yoshikawa Y.
Department of Biomedical Science
Graduate School of Agricultural and Life Sciences
The University of Tokyo
1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan.
aa07197@mail.ecc.u-tokyo.ac.jp
Diabetes Metab Res Rev. 2004 May-Jun;20(3):211-8.
Abstract
BACKGROUND: In our recent report,
probucol treatment ameliorated glucose intolerance and increased the
insulin-positive area in the pancreas of streptozotocin (SZ)-induced
diabetic APA hamsters. The data suggested that the beneficial effects of
probucol treatment on beta-cell function might result from its additive
effect as an antioxidant. Here, we examined the antioxidant effects on
the beta-cell function in SZ-induced diabetic APA hamsters treated with
three different agents, N-acetyl Cysteine (NAC), aminoguanidine (AG)
and pyridoxamine (PM).
METHODS: The control (CB group) and diabetic (SZ group) hamsters were
treated with NAC, AG, or pyridoxamine for four weeks from several days
after SZ injection.
RESULTS: Non-fasting plasma glucose and glycoalbumin levels were
significantly reduced in SZ animals by NAC or pyridoxamine treatment.
Glucose tolerance test revealed that fasting plasma glucose levels of
SZNAC and SZ pyridoxamine animals were low, similar to the corresponding
control animals. Thirty minutes after glucose injection,
amelioration in the plasma glucose levels of SZNAC and SZ pyridoxamine
animals was observed. Immunohistochemistry revealed that the
pancreata of SZNAC, SZAG and SZ pyridoxamine animals showed
significantly higher percentages of insulin-positive area than those of
non-treated SZ animals. The plasma 8OHdG and malondialdehyde plus
4-hydroxy-2-nonenal (4HNE) levels were significantly decreased
especially in SZNAC and SZPM animals. 4HNE-positive cells stained by
anti-4HNE antibody were reduced in the islets of each agent-treated
animal. SZNAC and SZ pyridoxamine animals showed significantly increased
beta-cell proliferation determined by insulin and BrdU double staining. All SZ groups treated with NAC, AG, or pyridoxamine had the high
expression levels of Reg and INGAP, which are known to be expressed in
regenerating islets.
CONCLUSIONS: These data suggest that N-acetyl Cysteine and
pyridoxamine treatment of SZ-injected diabetic hamsters reduces
oxidative stress and restores beta-cell function, but that
aminoguanidine treatment has little beneficial effect on the diabetic
conditions of SZ-injected hamsters.
