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Pro‐oxidant challenge in vivo provokes the onset of NIDDM in the insulin resistant obese Zucker rat
Author(s) -
Laight David W,
Desai Kaushik M,
Gopaul Nitin K,
Änggård Erik E,
Carrier Martin J
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702801
Subject(s) - medicine , endocrinology , insulin resistance , insulin , diabetes mellitus , in vivo , oxidative stress , hyperinsulinemia , biology , microbiology and biotechnology
We investigated the ability of an acute pro‐oxidant challenge in vivo to deteriorate glycaemic control and insulin action in the obese Zucker rat, a model of insulin resistance associated with oxidant stress. In obese animals, the daily administration for 1 week of hydroquinone (HQ) in combination with L ‐buthionine sulphoximine (BSO), elevated fasting plasma glycaemia and insulinaemia and markedly aggravated i.v. glucose‐stimulated hyperinsulinaemia without significantly affecting i.v. glucose tolerance, suggesting exacerbated insulin resistance. Intermediate effects on hyperinsulinaemia in obese animals were determined with HQ treatment alone while BSO treatment alone had no effect. In contrast, none of the pro‐oxidant treatments affected age‐matched, insulin sensitive, lean Zucker rats. Our data therefore demonstrate for the first time, a vulnerability to deterioration in insulin action in an established insulin resistant state following an environmental pro‐oxidative insult. This may have relevance in the conversion of insulin resistance syndrome (IRS) to non‐insulin dependent diabetes mellitus (NIDDM). British Journal of Pharmacology (1999) 128 , 269–271; doi: 10.1038/sj.bjp.0702801