Studies of Insulin Resistance in the Streptozotocin Diabetic and BB Rat: Activation of Low Km cAMP Phosphodiesterase by Insulin

Solomon, Solomon S.; Deaton, Jane; Harris, G.E.; Smoake, J.A.

doi:10.1097/00000441-198906000-00008

Cited by 10 publications

(1 citation statement)

References 18 publications

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“…The STZ-DM rat is a common model for the study of type 1 diabetes, but differs from human diabetic pathophysiology in its insulin resistance (Solomon et al, 1989). The average type 1 diabetic patient requires insulin substitution in the range of 0.5 to 1.0 IE/kg BW per day (Weintrob et al, 2003), in order to achieve normoglycaemia, compared to the insulin doses of 5 IE/kg BW per day, which were administered in the present study without rendering the rats normoglycaemic.…”

Section: Discussionmentioning

confidence: 99%

Improvement of insulin response in the streptozotocin model of insulin-dependent diabetes mellitus. Insulin response with and without a long-acting insulin treatment

Nordquist

Sjöquist

2009

Animal

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Streptozotocin-induced diabetes mellitus (STZ-DM) in rats is a model of type 1 diabetes, which is commonly used to study diabetes, but differs from human diabetic pathophysiology in its insulin resistance. An STZ-DM rat can be administered five times the dose of insulin compared to that of a diabetic patient. Thus, attaining normoglycaemia in STZ-DM rats with insulin injections is complicated, and it involves an obvious risk of overdosing before getting a response. This study was designed to investigate whether suboptimal treatment with long-acting insulin restores insulin sensitivity in the STZ-DM rat, and thus an approach to more closely mimic the human condition. Male Sprague-Dawley rats were made diabetic by means of a single intravenous injection of STZ (55 mg/kg body weight (BW)), resulting in an increase in blood glucose (BG) from 6.5 6 0.2 to 22.5 6 1.0 mmol/l ( P < 0.05) within 24 h. After treating the STZ-DM rats with vehicle for 14 days, BG was 26.1 6 1.1 mmol/l, and the response to a single injection of fast-acting insulin (Humalog, 5 IE/kg BW) was a 23% reduction in BG. Thereafter, the rats were treated daily with a suboptimal dose of long-acting insulin for a total of 7 days (Insulatard, 5 IE/kg per day), which resulted in a BG level of 19.4 6 2.7. The response to fast-acting insulin after the suboptimal treatment was a 61% reduction in BG. Thereafter, the animals were vehicle-treated for another 7 days, which resulted in a response to fast-acting insulin similar to the initial values (234%). Furthermore, the group treated with suboptimal doses of long-acting insulin had a longer duration of the reduction in BG (150 min, as opposed to 90 min in the vehicle-treated groups). We conclude that the development of a decreased insulin response occurs rapidly within the first 2 weeks after the onset of diabetes in STZ-DM rats. This leads to a brief and significantly reduced decrease in BG when fast-acting insulin is administered. The insulin response is increased by treatment with suboptimal doses of long-acting insulin, but rapidly decreases again when treatment is withdrawn. Regular administration of suboptimal insulin doses may provide an approach to eliminate the effects of a lowered insulin response.

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Section: Discussionmentioning

confidence: 99%