Pro‐oxidant challenge in vivo provokes the onset of NIDDM in the insulin resistant obese Zucker rat

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 w...

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Published in:British journal of pharmacology 1999-09, Vol.128 (2), p.269-271
Main Authors: Laight, David W, Desai, Kaushik M, Gopaul, Nitin K, Änggård, Erik E, Carrier, Martin J
Format: Article
Language:English
Subjects:
Animals
Antimetabolites - pharmacology
Antioxidants - pharmacology
Biological and medical sciences
Blood Glucose - metabolism
Body Weight - drug effects
Buthionine Sulfoximine - pharmacology
Diabetes Mellitus, Type 2 - chemically induced
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Glucose Tolerance Test
Glutathione - antagonists & inhibitors
Hydroquinones - pharmacology
Insulin - blood
Insulin resistance
Insulin Resistance - physiology
Male
Medical sciences
NIDDM
obese Zucker rat
Obesity - complications
Obesity - genetics
oxidant stress
Oxidants - toxicity
Rats
Rats, Zucker
Special Reports
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Summary: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
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0702801