Quinnipiac University Frank H Netter MD School of Medicine, North Haven, CT, USA.
Burke Neurological Institute, 785 Mamaroneck Ave, White Plains, NY, 10605, USA.
Dig Dis Sci. 2023 Jul;68(7):2963-2974. doi: 10.1007/s10620-023-07913-5. Epub 2023 Mar 15.
Diabetes Mellitus causes a systemic oxidative stress due in part to the hyperglycemia and the reactive oxygen species generated. Up to 75% of diabetic patients present with an autonomic neuropathy affecting the Enteric Nervous System. Deficits in the human population are chronic dysmotilities with either increased (i.e., constipation) or decreased (i.e., diarrhea) total gastrointestinal transit times. These are recapitulated in the streptozocin-induced diabetic rat, which is a model of Type I Diabetes Mellitus.
Examine the effects that a precursor of nicotinamide adenosine dinucleotide (NAD), nicotinamide riboside (NR), had on the development of dysmotility in induced diabetic rats and if fecal microbiota transplant (FMT) could produce the same results.
Utilizing a 6-week treatment paradigm, NR was administered intraperitoneally every 48 h. Total gastrointestinal transit time was assessed weekly utilizing the carmine red method. Three weeks following hyperglycemic induction, FMT was performed between NR-treated animals and untreated animals.
There is improvement in overall gastrointestinal transit time with the use of NR. 16S microbiome sequencing demonstrated decreased alpha and beta diversity in induced diabetic rats without change in animals receiving FMT. Improvements in myenteric plexus ganglia density in small and large intestines in diabetic animals treated with NR were seen.
NR treatment led to functional improvement in total gastrointestinal transit time in induced diabetic animals. This was associated with neuroprotection in the myenteric plexuses of both small and large intestines of induced diabetic rats. This represents an important first step in showing NR's benefit as a treatment for diabetic enteric neuropathy. Streptozocin-induced diabetic rats have improved transit times and increased myenteric plexus ganglia density when treated with intraperitoneal nicotinamide riboside.
糖尿病会导致全身性氧化应激，部分原因是高血糖和产生的活性氧。多达 75%的糖尿病患者会出现自主神经病变，影响肠神经系统。在人口中，缺陷表现为慢性运动障碍，总胃肠道通过时间增加（即便秘）或减少（即腹泻）。这些在链脲佐菌素诱导的糖尿病大鼠中得到了重现，该大鼠是 1 型糖尿病的模型。
研究烟酰胺腺嘌呤二核苷酸（NAD）前体烟酰胺核苷（NR）对诱导糖尿病大鼠运动障碍发展的影响，以及粪便微生物群移植（FMT）是否能产生相同的结果。
利用 6 周的治疗方案，每 48 小时通过腹腔内给药 NR。每周利用胭脂红法评估总胃肠道通过时间。在高血糖诱导后 3 周，在 NR 治疗动物和未治疗动物之间进行 FMT。
使用 NR 可改善整体胃肠道通过时间。16S 微生物组测序显示，在未接受 FMT 的动物中，诱导性糖尿病大鼠的 alpha 和 beta 多样性降低。NR 治疗的糖尿病动物的小肠和大肠的肌间神经丛神经节密度增加。
NR 治疗可改善诱导性糖尿病动物的总胃肠道通过时间。这与 NR 治疗的诱导性糖尿病大鼠的肌间神经丛的神经保护有关。这代表了 NR 作为治疗糖尿病肠神经病的一种治疗方法的重要第一步。用腹腔内烟酰胺核苷治疗链脲佐菌素诱导的糖尿病大鼠可改善通过时间并增加肌间神经丛神经节密度。
