, Volume 38, Issue 9, pp 1033-1041

Insulin resistance in skeletal muscle of the male Otsuka Long-Evans Tokushima Fatty rat, a new model of NIDDM

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Summary

The Otsuka Long-Evans Tokushima Fatty rat is a new inbred obese strain with a late onset and chronic course of spontaneous hyperglycaemia in the male, and is considered to be a model of non-insulin-dependent diabetes mellitus [1, 2]. Fat distribution analysis showed a typical accumulation of intra-abdominal visceral fat in Otsuka Long-Evans Tokushima Fatty rats compared with a control strain, Long-Evans Tokushima Otsuka rats. To examine the insulin sensitivity of Otsuka Long-Evans Tokushima Fatty rats, we performed euglycaemic hyperinsulinaemic clamp experiments in vivo in rats under anaesthesia on this strain and on Long-Evans Tokushima Otsuka rats. The Otsuka Long-Evans Tokushima Fatty rats showed lower values for the glucose infusion rate (60% of the control at 12 weeks old and 20–30% of the control at 18, 24, 30 and 39 weeks old) than age-matched controls, indicating the development of insulin resistance with age. Hindlimb perfusion experiments in vitro also showed a 45% decrease of insulin-stimulated glucose uptake in Otsuka Long-Evans Tokushima Fatty rats in the diabetic stage. These results indicate that insulin resistance exists in the skeletal muscle of Otsuka Long-Evans Tokushima Fatty rats. To obtain information on the mechanism of insulin resistance in the skeletal muscle of Otsuka Long-Evans Tokushima Fatty rats, the insulin binding, autophosphorylation and tyrosine kinase activity of their partially-purified insulin receptors in vitro were compared with those from control rats. The results showed no marked differences in these insulin receptor functions between diabetic and control rats. These results suggest that it is unlikely that severe insulin-receptor dysfunction is responsible for the insulin resistance in the skeletal muscle of Otsuka Long-Evans Tokushima Fatty rats.