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，很少有研究调查在正常血糖或糖尿病前期代谢综合征动物模型中是否会出现微小的感觉神经功能障碍。对8至36周龄肥胖的雄性Zucker大鼠和8至36周龄的雄性Zucker糖尿病肥胖(ZDF)大鼠的热和机械伤害性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周龄时都表现出代偿性高胰岛素血症，并在出现明显的高血糖之前出现热痛觉过敏。这些动物还表现出从热痛觉过敏到痛觉过敏的进展，这种进展发生得更快，与ZDF大鼠胰腺胰岛素分泌比肥胖Zucker大鼠更快的下降相吻合。基于这些发现，我们得出结论，有或没有代偿性高胰岛素血症的代谢综合征与具有不同表型的伤害性功能障碍有关，与血糖水平无关。

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.