Hossain Md Jakir, Kendig Michael D, Wild Brandon M, Issar Tushar, Krishnan Arun V, Morris Margaret J, Arnold Ria
School of Medical Sciences, UNSW Sydney, Sydney NSW 2052, Australia.
Prince of Wales Clinical School, UNSW Sydney, Sydney NSW 2052, Australia.
Biomedicines. 2020 Aug 28;8(9):313. doi: 10.3390/biomedicines8090313.
Peripheral neuropathy (PN) is a debilitating complication of diabetes that affects >50% of patients. Recent evidence suggests that obesity and metabolic disease, which often precede diabetes diagnosis, may influence PN onset and severity. We examined this in a translationally relevant model of prediabetes induced by a cafeteria (CAF) diet in Sprague-Dawley rats ( = 15 CAF versus = 15 control). Neuropathy phenotyping included nerve conduction, tactile sensitivity, intraepidermal nerve fiber density (IENFD) and nerve excitability testing, an in vivo measure of ion channel function and membrane potential. Metabolic phenotyping included body composition, blood glucose and lipids, plasma hormones and inflammatory cytokines. After 13 weeks diet, CAF-fed rats demonstrated prediabetes with significantly elevated fasting blood glucose, insulin and impaired glucose tolerance as well as obesity and dyslipidemia. Nerve conduction, tactile sensitivity and IENFD did not differ; however, superexcitability was significantly increased in CAF-fed rats. Mathematical modeling demonstrated this was consistent with a reduction in sodium-potassium pump current. Moreover, superexcitability correlated positively with insulin resistance and adiposity, and negatively with fasting high-density lipoprotein cholesterol. In conclusion, prediabetic rats over-consuming processed, palatable foods demonstrated altered nerve function that preceded overt PN. This work provides a relevant model for pathophysiological investigation of diabetic complications.
周围神经病变（PN）是糖尿病一种使人衰弱的并发症，影响超过50%的患者。最近的证据表明，肥胖和代谢性疾病往往在糖尿病诊断之前出现，可能会影响PN的发病和严重程度。我们在一个与转化相关的糖尿病前期模型中对此进行了研究，该模型由给予斯普拉格-道利大鼠自助餐厅（CAF）饮食诱导（n = 15只CAF饮食组大鼠与n = 15只对照组大鼠）。神经病变表型分析包括神经传导、触觉敏感性、表皮内神经纤维密度（IENFD）以及神经兴奋性测试，神经兴奋性测试是一种对离子通道功能和膜电位的体内测量方法。代谢表型分析包括身体组成、血糖和血脂、血浆激素以及炎性细胞因子。经过13周的饮食干预后，给予CAF饮食的大鼠出现糖尿病前期症状，空腹血糖、胰岛素显著升高，糖耐量受损，同时伴有肥胖和血脂异常。神经传导、触觉敏感性和IENFD没有差异；然而，给予CAF饮食的大鼠超兴奋性显著增加。数学建模表明，这与钠钾泵电流降低一致。此外，超兴奋性与胰岛素抵抗和肥胖呈正相关，与空腹高密度脂蛋白胆固醇呈负相关。总之，过度食用加工过的可口食物的糖尿病前期大鼠在明显的PN出现之前就表现出神经功能改变。这项工作为糖尿病并发症的病理生理研究提供了一个相关模型。
