Wu Gaojue, Li Fei, Li Yan, Li Shiying, Alam Md Jahangir, Chen Jiande D Z
Division of Gastroenterology and Hepatology, School of Medicine, University of Michigan, Ann Arbor, Michigan, United States.
Am J Physiol Gastrointest Liver Physiol. 2025 Apr 1;328(4):G386-G398. doi: 10.1152/ajpgi.00278.2024. Epub 2025 Feb 24.
The abnormalities of gastrointestinal (GI) slow waves play key roles in the pathophysiology of diabetic gastroparesis, which is highly prevalent in type 2 diabetes (T2D). Although relatively well-investigated in diabetic enteric neuropathy, abnormalities and progressive impairments of gastric slow waves (GSWs) and duodenal slow waves (DSWs) are underinvestigated during the progression of T2D. The aim of this study was to explore alterations in GSW and DSW during the development of diabetes induced by high-fat diet (HFD) followed by a low dose of streptozotocin (STZ). Weekly recordings of slow waves from healthy, prediabetic to diabetes stages exhibited a progressively decreased percentage of normal slow waves (%NSW) starting after HFD feeding (prediabetic stage) in the fasting state and starting after STZ injection (diabetic stage) in the postprandial state. The postprandial increase in the power of slow waves observed in normal control rats was absent starting from 2 wk after HFD and persisted after STZ. The mechanism might be attributed to both progressively increased blood glucose (BG) and impaired autonomic function in view of the following results: ) the %NSW was negatively correlated with the fasting BG; ) during the oral glucose tolerance test, %NSW of DSW and BG exhibited a positive correlation in rats with hemoglobin A1C (HbA1C) < 5.0%, but a negative correlation in rats with HbA1C ≥ 5.0%; and ) in comparison with baseline (healthy stage) of the same cohort, plasma pancreatic polypeptide (reflecting vagal activity) was progressively decreased, whereas plasma norepinephrine (reflecting sympathetic activity) was progressively increased. This study recorded the progressive impairment in the regularity of gastric and duodenal slow waves in a rat model mimicking the progression to type 2 diabetes including the stage of health, prediabetic stage, and diabetes. The progressive impairment in gastric/duodenal slow waves might be attributed to the progressive increase in blood glucose and impairment in autonomic function.
胃肠道（GI）慢波异常在糖尿病胃轻瘫的病理生理学中起关键作用，糖尿病胃轻瘫在2型糖尿病（T2D）中非常普遍。尽管在糖尿病性肠神经病变方面已有相对充分的研究，但在T2D进展过程中，胃慢波（GSWs）和十二指肠慢波（DSWs）的异常及进行性损害尚未得到充分研究。本研究的目的是探讨在高脂饮食（HFD）后给予低剂量链脲佐菌素（STZ）诱导的糖尿病发展过程中GSW和DSW的变化。从健康、糖尿病前期到糖尿病阶段每周记录慢波，结果显示，在空腹状态下，自HFD喂养后（糖尿病前期）以及在餐后状态下自STZ注射后（糖尿病阶段），正常慢波百分比（%NSW）逐渐下降。正常对照大鼠中观察到的餐后慢波功率增加，从HFD后2周开始消失，并在STZ注射后持续存在。鉴于以下结果，其机制可能归因于血糖（BG）逐渐升高和自主神经功能受损：）%NSW与空腹BG呈负相关；）在口服葡萄糖耐量试验中，糖化血红蛋白（HbA1C）<5.0%的大鼠中，DSW的%NSW与BG呈正相关，但在HbA1C≥5.0%的大鼠中呈负相关；）与同一队列的基线（健康阶段）相比，血浆胰多肽（反映迷走神经活动）逐渐减少，而血浆去甲肾上腺素（反映交感神经活动）逐渐增加。本研究记录了在模拟向2型糖尿病进展的大鼠模型中，包括健康阶段（健康）、糖尿病前期和糖尿病阶段，胃和十二指肠慢波规律性的进行性损害。胃/十二指肠慢波的进行性损害可能归因于血糖的逐渐升高和自主神经功能的损害。
