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Effects of pro‐oxidant treatment on the progression of prediabetes in SHROB rats
Author(s) -
Ernsberger Paul,
Theodorou Maria,
Edwards Simone,
Koletsky Richard J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1153.7
Subject(s) - oxidative stress , prediabetes , endocrinology , medicine , diabetes mellitus , postprandial , type 2 diabetes , buthionine sulfoximine , insulin resistance , glutathione , antioxidant , chemistry , biochemistry , enzyme
The spontaneously hypertensive obese (SHROB) rat is a model of prediabetes characterized by normal fasting and high postprandial glucose and insulin resistance. Oxidative stress, through the damaging effects of oxygen radicals, may contribute to the onset of diabetes. We induced oxidative stress in SHROB with a combination of a pro‐oxidant agent, hydroquinone, and a glutathione depleting agent, L‐buthionine sulfoximine (both 50 mg/kg ip). Oxidative stress is increased in untreated SHROB rats, as indicated by a 3‐fold increases in levels of peroxides in the plasma as well as in the kidney. Antioxidant antihypertensive therapy with captopril lowered oxidative stress in SHROB by about 2‐fold. Pro‐oxidant injection increased plasma peroxide levels within 1h and returned to baseline within 24h. Induction of further oxidative stress in prediabetic SHROB causes diabetes within two days of daily treatment, as indicated by morning blood glucose values averaging over 200 mg/dl versus about 100 mg/dl in control SHROB. Glucose fell to baseline within 3d, but glucose tolerance was significantly impaired. Food intake and body weight were not affected. The SHROB rat subjected to oxidative stress is a potential model to study the onset of Type 2 diabetes, and supports the hypothesis that oxidative stress may be a trigger for diabetes onset in susceptible individuals.