• Diabetes Metab. Res. Rev. · Nov 2008

    Time course of pain sensation in rat models of insulin resistance, type 2 diabetes, and exogenous hyperinsulinaemia.

    • Kazuhiro Sugimoto, Irena B Rashid, Keiya Kojima, Masaru Shoji, Jutaro Tanabe, Naoki Tamasawa, Toshihiro Suda, and Minoru Yasujima.
    • Department of Laboratory Medicine, Hirosaki University Graduate School of Medicine, Zaifu-cho, Hirosaki, Japan. sugimoto@cc.hirosaki-u.ac.jp <sugimoto@cc.hirosaki-u.ac.jp>
    • Diabetes Metab. Res. Rev. 2008 Nov 1; 24 (8): 642-50.

    BackgroundSmall sensory fibre dysfunction has been recently recognized as a component of impaired glucose tolerance and insulin resistance (IR) syndrome. However, few studies have investigated whether small sensory fibre dysfunction develops in normoglycaemic or pre-diabetic animal models of IR and/or hyperinsulinaemia. In addition, scant information is available on the metabolic features of IR in relation to small sensory fibre dysfunction due to the progressive failure of beta cells to compensate for IR during the development of frank diabetes.MethodsLongitudinal trends for thermal and mechanical nociceptive responses were assessed in 8-36-week-old male obese Zucker rats, 8-36-week-old male Zucker diabetic fatty (ZDF) rats, and 10-39-week-old male Wistar rats that continued to receive exogenous insulin (2-4 U/day) from subcutaneously implanted insulin pellets. Data were compared with the metabolic disorders in these rats.ResultsBoth obese Zucker and ZDF rats at 8 weeks of age showed compensatory hyperinsulinaemia and developed thermal hyperalgesia prior to the onset of overt hyperglycaemia. These animals also exhibited progression from thermal hyperalgesia to hypoalgesia, which occurred more rapidly and coincided with a more rapid decline in pancreatic insulin secretion in ZDF rats than in obese Zucker rats. Non-diabetic rats treated with insulin tended to show thermal and mechanical hypoalgesia that was detectable 12-20 weeks after treatment.ConclusionIn addition to insulin treatment, IR with or without compensatory hyperinsulinaemia is associated with nociceptive dysfunction of different phenotypes, independent of glycaemic levels.Copyright 2008 John Wiley & Sons, Ltd.

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