Sugimoto Kazuhiro, Rashid Irena B, Kojima Keiya, Shoji Masaru, Tanabe Jutaro, Tamasawa Naoki, Suda Toshihiro, Yasujima Minoru
Department of Laboratory Medicine, Hirosaki University Graduate School of Medicine, Zaifu-cho, Hirosaki, Japan.
Diabetes Metab Res Rev. 2008 Nov-Dec;24(8):642-50. doi: 10.1002/dmrr.903.
Small 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.
Longitudinal 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.
Both 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.
In addition to insulin treatment, IR with or without compensatory hyperinsulinaemia is associated with nociceptive dysfunction of different phenotypes, independent of glycaemic levels.
小感觉纤维功能障碍最近被认为是糖耐量受损和胰岛素抵抗（IR）综合征的一个组成部分。然而，很少有研究调查在IR和/或高胰岛素血症的正常血糖或糖尿病前期动物模型中是否会出现小感觉纤维功能障碍。此外，由于在显性糖尿病发展过程中β细胞逐渐无法补偿IR，关于IR与小感觉纤维功能障碍相关的代谢特征的信息很少。
对8 - 36周龄的雄性肥胖Zucker大鼠、8 - 36周龄的雄性Zucker糖尿病脂肪（ZDF）大鼠以及10 - 39周龄的雄性Wistar大鼠进行纵向热和机械伤害性反应评估，这些Wistar大鼠通过皮下植入胰岛素丸持续接受外源性胰岛素（2 - 4 U/天）。将数据与这些大鼠的代谢紊乱情况进行比较。
8周龄的肥胖Zucker大鼠和ZDF大鼠均表现出代偿性高胰岛素血症，并在明显高血糖发作之前出现热痛觉过敏。这些动物还表现出从热痛觉过敏发展为痛觉减退，ZDF大鼠比肥胖Zucker大鼠发生得更快，且与胰腺胰岛素分泌的更快下降同时发生。接受胰岛素治疗的非糖尿病大鼠倾向于表现出热和机械性痛觉减退，在治疗后12 - 20周可检测到。
除胰岛素治疗外，伴有或不伴有代偿性高胰岛素血症的IR与不同表型的伤害性感受功能障碍相关，与血糖水平无关。
