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Improvement of insulin response in the streptozotocin model of insulin-dependent diabetes mellitus.: Insulin response with and without a long-acting insulin treatment
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi. (Nordquist)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi.
2009 (English)In: Animal, ISSN 1751-7311, Vol. 3, no 5, 685-689 p.Article in journal (Refereed) Published
Abstract [en]

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 +/- 0.2 to 22.5 +/- 1.0 mmol/l (P <= 0.05) within 24h. After treating the STZ-DM rats with vehicle for 14 days, BG was 26.1 +/- 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 +/- 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 (-34%).   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 tast-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.

Place, publisher, year, edition, pages
Cambridge university press , 2009. Vol. 3, no 5, 685-689 p.
Keyword [en]
insulin response, reversal, STZ-DM, diabetes, animal model
National Category
Medical and Health Sciences
Research subject
URN: urn:nbn:se:uu:diva-119872DOI: 10.1017/S175173110800387XISI: 000265335600008OAI: oai:DiVA.org:uu-119872DiVA: diva2:301103
Available from: 2010-03-02 Created: 2010-03-02 Last updated: 2011-11-17Bibliographically approved

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