Molecular and pathogenic mechanisms for peripheral neuropathy associated with metabolic syndrome

小感觉纤维功能障碍最近被认为是糖耐量受损和代谢综合征的一个组成部分。然而，很少有研究调查小感觉纤维功能障碍是否发生在血糖正常或糖尿病前期代谢综合征动物模型中。在8- 36周龄的雄性肥胖Zucker大鼠和8- 36周龄的雄性糖尿病肥胖（ZDF）大鼠中，对热和机械伤害反应的纵向趋势进行了评估。将数据与这些大鼠的代谢紊乱进行比较。肥胖的Zucker和ZDF大鼠在8周龄时均表现出代偿性高胰岛素血症，并在明显高血糖发作前出现热痛觉过敏。这些动物也表现出从热痛觉过敏到痛觉过敏的进展，与肥胖的Zucker大鼠相比，ZDF大鼠发生得更快，并且与胰腺胰岛素分泌下降更快。基于这些发现，我们得出结论，代偿性高胰岛素血症或不代偿性高胰岛素血症的代谢综合征与具有不同表型的痛觉功能障碍相关，独立于血糖水平。

Small sensory fiber dysfunction has recently been recognized as a component of impaired glucose tolerance and metabolic syndrome. However, few studies have investigated whether small sensory fiber dysfunction develops in normoglycemic or prediabetic animal models with metabolic syndrome. Longitudinal trends for thermal and mechanical nociceptive responses were assessed in 8-to 36-week-old male obese Zucker rats, 8-to 36-week-old male Zucker diabetic fatty (ZDF) rats. Data were compared with metabolic disorders in these rats. Both obese Zucker and ZDF rats at 8 weeks of age showed compensatory hyperinsulinemia and developed thermal hyperalgesia prior to the onset of overt hyperglycemia. These animals also exhibited progression from thermal hyperalgesia to hyperalgesia, which occurred more rapidly and coincided with a more rapid decline in pancreatic insulin secretion in ZDF rats than in obese Zucker rats. Based on these findings we conclude that metabolic syndrome with or without compensatory hyperinsulinemia is associated with nociceptive dysfunction having different phenotypes, independently of glycemic levels.