Insulin Resistance in Rat Skeletal Muscle Induced by Acute Glucose Infusion Is Not Dependent on Oxidative Stress.

Hoy, Andrew J.; Bruce, Clinton R.; Turner, Nigel; James, David E.; Cooney, Gregory J.; Kraegen, Edward W.

Hyperglycemia contributes directly to the development of diabetes complications via mechanisms thought to involve increased oxidative stress. The aim of the present study was to investigate whether oxidative stress plays a significant role in the onset of skeletal muscle insulin resistance in rats caused by glucose infusion for more than 3h. Male rats were infused with saline (control) or glucose to increase and maintain blood glucose at approximately 10mM. Blood was sampled every 30min for glucose and insulin. Animals were sacrificed at 1h, 3h and 5h to determine changes associated with the development of insulin resistance. In one cohort of animals the antioxidant taurine (0.35mg·kg[sup -1]⋅min[sup -1]) was co-infused with glucose for 5h. Dihydroethidium (DHE), which fluoresces after combining with reactive oxygen species, and glucose tracers were given as a bolus for the final hour. Aconitase, Superoxide Dismutase, Glutathione Peroxidase and reductase activity, as well as protein carbonyls were determined in skeletal muscle. Acute glucose infusion increased circulating insulin to a new steady state level 8-fold above basal. The glucose infusion rate required to maintain blood glucose at 10mM significantly decreased (P < 0.001) between 3h and 5h of glucose infusion indicating the development of insulin resistance. Muscle glucose uptake was also significantly reduced (40%, P < 0.05) between 3h and 5h of glucose infusion. There was no change in superoxide sensitive aconitase activity, antioxidant enzyme activity, protein carbonyls, or DHE fluorescence over the same period in which insulin resistance developed. Co-infusion of taurine reduced DHE fluorescence, but had no effect on decreased glucose uptake in muscle. Although 5h of hyperglycemia produced insulin resistance in skeletal muscle, there was no evidence that this was accompanied by a change in markers of oxidative stress. Furthermore, administration of an antioxidant did not alleviate the insulin resistance in muscle produced by hyperglycemia. These results suggest that oxidative stress is not involved in the development of skeletal muscle insulin resistance seen after acute (5h) hyperglycemia.

HYPERGLYCEMIA; DIABETES complications; OXIDATIVE stress; MUSCULOSKELETAL system; INSULIN resistance; GLUCOSE; BLOOD sugar

Diabetes, 2007, Vol 56, pA341

0012-1797

Academic Journal