Zhou Shi-Yi, Lu Yuan-Xu, Owyang Chung
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Am J Physiol Gastrointest Liver Physiol. 2008 May;294(5):G1158-64. doi: 10.1152/ajpgi.00067.2008. Epub 2008 Mar 20.
Hyperglycemia has a profound effect on gastric motility. However, little is known about the site and mechanism that sense alteration in blood glucose level. The identification of glucose-sensing neurons in the nodose ganglia led us to hypothesize that hyperglycemia acts through vagal afferent pathways to inhibit gastric motility. With the use of a glucose-clamp rat model, we showed that glucose decreased intragastric pressure in a dose-dependent manner. In contrast to intravenous infusion of glucose, intracisternal injection of glucose at 250 and 500 mg/dl had little effect on intragastric pressure. Pretreatment with hexamethonium, as well as truncal vagotomy, abolished the gastric motor responses to hyperglycemia (250 mg/dl), and perivagal and gastroduodenal applications of capsaicin significantly reduced the gastric responses to hyperglycemia. In contrast, hyperglycemia had no effect on the gastric contraction induced by electrical field stimulation or carbachol (10(-5) M). To rule out involvement of serotonergic pathways, we showed that neither granisetron (5-HT(3) antagonist, 0.5 g/kg) nor pharmacological depletion of 5-HT using p-chlorophenylalanine (5-HT synthesis inhibitor) affected gastric relaxation induced by hyperglycemia. Lastly, N(G)-nitro-L-arginine methyl ester (L-NAME) and a VIP antagonist each partially reduced gastric relaxation induced by hyperglycemia and, in combination, completely abolished gastric responses. In conclusion, hyperglycemia inhibits gastric motility through a capsaicin-sensitive vagal afferent pathway originating from the gastroduodenal mucosa. Hyperglycemia stimulates vagal afferents, which, in turn, activate vagal efferent cholinergic pathways synapsing with intragastric nitric oxide- and VIP-containing neurons to mediate gastric relaxation.
高血糖对胃动力有深远影响。然而，关于感知血糖水平变化的部位和机制却知之甚少。在结状神经节中发现葡萄糖敏感神经元，这使我们推测高血糖通过迷走神经传入途径抑制胃动力。利用葡萄糖钳夹大鼠模型，我们发现葡萄糖以剂量依赖的方式降低胃内压。与静脉输注葡萄糖不同，脑池内注射250和500mg/dl的葡萄糖对胃内压几乎没有影响。六甲铵预处理以及迷走神经干切断术消除了胃对高血糖（250mg/dl）的运动反应，辣椒素经迷走神经周围和胃十二指肠应用显著降低了胃对高血糖的反应。相反，高血糖对电场刺激或卡巴胆碱（10⁻⁵M）诱导的胃收缩没有影响。为排除5-羟色胺能途径的参与，我们发现格拉司琼（5-HT₃拮抗剂，0.5g/kg）以及使用对氯苯丙氨酸（5-HT合成抑制剂）对5-HT进行药理学耗竭均不影响高血糖诱导的胃舒张。最后，N(G)-硝基-L-精氨酸甲酯（L-NAME）和一种VIP拮抗剂各自部分降低了高血糖诱导的胃舒张，联合使用则完全消除了胃反应。总之，高血糖通过起源于胃十二指肠黏膜的辣椒素敏感迷走神经传入途径抑制胃动力。高血糖刺激迷走神经传入纤维，进而激活与胃内含一氧化氮和VIP的神经元形成突触的迷走神经传出胆碱能途径，以介导胃舒张。
