Saberi H, Mehranfard N, Rezazadeh H, Ghasemi M
School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Nanokadeh Darooee Samen Private Joint Stock Company, Urmia 5715793731, Iran.
Arch Razi Inst. 2024 Jun 30;79(3):601-608. doi: 10.32592/ARI.2024.79.3.601. eCollection 2024 Jun.
Gastrointestinal dysfunction is a severe and common complication in diabetic patients. Some evidence shows that gamma-aminobutyric acid (GABA) and glutamate contribute to diabetic gastrointestinal abnormalities. Therefore, we examined the impact of prolonged treatment with insulin and magnesium supplements on the expression pattern of GABA type A (GABA-A), GABA-B, and N-methyl-D-aspartate (NMDA) glutamate receptors as well as nitric oxide synthase 1 (NOS-1) in the stomach of type 2 diabetic rats. Twenty-four male Wistar rats were randomized to four groups (six rats each): 1) control, 2) type 2 diabetes: rats fed with a high-fat diet for three months + a low dose of streptozotocin (35 mg/kg), 3) type 2 diabetes + magnesium, and 4) type 2 diabetes + insulin. The expression of NOS-1, GABA-A, GABA-B, and NMDA receptors was detected using western blotting. The NOS-1 expression was substantially diminished (P<0.01), while the expression of GABA-A (P<0.001), GABA-B (P<0.001), and NMDA (P<0.001) receptors was enhanced in the stomach of diabetic rats relative to control. Treatment with magnesium and insulin improved NOS-1 expression in diabetic rats, although this effect was greater in magnesium treatment alone. Magnesium also restored the expression of GABA-A and GABA-B receptors in diabetic rats to control values. Moreover, insulin treatment improved GABA-A receptor expression in diabetic rats (P<0.05). No considerable alterations were detected in NMDA receptor levels in the treatment groups. The results suggest a significant role of magnesium and insulin in improving gastric motility and secretory disorders associated with diabetes through modifying the expression of GABAergic receptors.
胃肠功能障碍是糖尿病患者严重且常见的并发症。一些证据表明，γ-氨基丁酸（GABA）和谷氨酸与糖尿病性胃肠异常有关。因此，我们研究了胰岛素和镁补充剂长期治疗对2型糖尿病大鼠胃中GABA A型（GABA-A）、GABA B型（GABA-B）和N-甲基-D-天冬氨酸（NMDA）谷氨酸受体以及一氧化氮合酶1（NOS-1）表达模式的影响。将24只雄性Wistar大鼠随机分为四组（每组6只）：1）对照组，2）2型糖尿病组：大鼠喂食高脂饮食三个月+低剂量链脲佐菌素（35 mg/kg），3）2型糖尿病+镁组，4）2型糖尿病+胰岛素组。采用蛋白质免疫印迹法检测NOS-1、GABA-A、GABA-B和NMDA受体的表达。与对照组相比，糖尿病大鼠胃中NOS-1表达显著降低（P<0.01），而GABA-A（P<0.001）、GABA-B（P<0.001）和NMDA（P<0.001）受体表达增强。镁和胰岛素治疗可改善糖尿病大鼠的NOS-1表达，尽管单独使用镁治疗的效果更显著。镁还可将糖尿病大鼠GABA-A和GABA-B受体的表达恢复至对照值。此外，胰岛素治疗可改善糖尿病大鼠GABA-A受体的表达（P<0.05）。各治疗组中NMDA受体水平未检测到明显变化。结果表明，镁和胰岛素通过调节GABA能受体的表达，在改善糖尿病相关的胃动力和分泌紊乱方面发挥重要作用。
