The streptozotocin-induced diabetes mellitus (STZ-DM) rat model is commonly used to study diabetes. However, it differs from human diabetes in its insulin resistance. This study was designed to elucidate if insufficient replacement with long-acting insulin improves the insulin sensitivity in the STZ-DM rat. Male Sprague-Dawley rats were injected with streptozotocin (55mg (kg body wt)-1), resulting in a sustained hyperglycaemia (22.5±1.0 mM) measured using a glucose oxidase method on blood obtained from the cut tips of the tails (10-15 μl). After treating the rats with vehicle for 14 days, their blood glucose (BG) had reached 26.1±1.1, and the response to an injection of fast-acting insulin (5 IE (kg body wt)-1) was investigated. Thereafter, the rats were treated with long-acting insulin for 7 days (5 IE (kg body wt)-1 day-1), whereby BG decreased to 19.4±2.7. The response to fast-acting insulin was again recorded. After treating the rats with vehicle for a last set of 7 days, BG had increased to 26.9±1.7. The effect of fast-acting insulin was investigated to evaluate if resistance had reoccurred. Animals were humanely killed at the end of the experiments. The reduction in BG was more pronounced when pre-treated with long-acting insulin for a week (Day 22, 61%) as compared to the untreated groups (Day 15 and 28, 23% and 34%, respectively). When pre-treated with long-acting insulin the rats had a longer duration of effect in response to fast-acting insulin (150 min, as opposed to 90 min in the vehicle-treated rats). There was no difference between the vehicle-treated rats (Day 15 and Day 28) in their response to fast-acting insulin. In summary, insulin resistance developed in the STZ-DM rats, leading to a both brief and modest response to fast-acting insulin. The insulin resistance was reversed by treatment with long-acting insulin, but rapidly redeveloped after ceasing treatment. This should be taken into consideration when using this animal model.
University of Bristol (2005) J Physiol 567P, C14
Oral Communications: Reversal and reoccurrence of insulin resistance in streptozotocin-treated, hyperglycaemic rats
Nordquist, Lina; Isaksson, Britta; Sjoquist, Mats;
1. Medical Cell Biology, Uppsala University, UPPSALA, Sweden.
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Where applicable, experiments conform with Society ethical requirements.