Long-term GABA Supplementation Regulates Diabetic Gastroenteropathy through GABA Receptor/trypsin-1/PARs/Akt/COX-2 Axis

IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Farzaneh Yazdanimoghaddam, Hossein Rezazadeh, Nepton Soltani, Nasrin Mehranfard, Azadesadat Hosseini Dastgerdi, Mahtab Ghanbari Rad, Maedeh Ghasemi
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引用次数: 0

Abstract

Aim. Molecular alterations of diabetic gastroenteropathy are poorly identified. This study investigates the effects of prolonged GABA supplementation on key protein expression levels of trypsin-1, PAR-1, PAR-2, PAR-3, PI3K, Akt, COX-2, GABAA, and GABAB receptors in the gastric tissue of type 2 diabetic rats (T2DM).

To induce T2DM, a 3-month high-fat diet and 35 mg/kg of streptozotocin was used. Twenty-four male Wistar rats were divided into 4 groups: (1) control, (2) T2DM, (3) insulin-treated (2.5 U/kg), and (4) GABA-treated (1.5 g/kg GABA). Blood glucose was measured weekly. The protein expressions were assessed using western blotting. Histopathological changes were examined by H&E and Masson’s staining.

Diabetic rats show reduced NOS1 and elevated COX-2 and trypsin-1 protein expression levels in gastric tissue. Insulin and GABA therapy restored the NOS1 and COX-2 levels to control values. Insulin treatment increased PI3K, Akt, and p-Akt and, decreased trypsin-1, PAR-1, PAR-2, and PAR-3 levels in the diabetic rats. Levels of GABAA and GABAB receptors normalized following insulin and GABA therapy. H&E staining indicated an increase in mucin secretion following GABA treatment.

These results suggest that GABA by acting on GABA receptors may regulate the trypsin-1/PARs/Akt/COX-2 pathway and thereby improve complications of diabetic gastroenteropathy.

Abstract Image

Abstract Image

长期补充 GABA 可通过 GABA 受体/胰蛋白酶-1/PARs/Akt/COX-2 轴调节糖尿病胃肠病。
目的:糖尿病胃肠病的分子改变尚未被明确。本研究探讨了长期补充 GABA 对 2 型糖尿病大鼠(T2DM)胃组织中胰蛋白酶-1、PAR-1、PAR-2、PAR-3、PI3K、Akt、COX-2、GABAA 和 GABAB 受体的关键蛋白表达水平的影响。将 24 只雄性 Wistar 大鼠分为 4 组:(1) 对照组;(2) T2DM 组;(3) 胰岛素处理组(2.5 U/kg);(4) GABA 处理组(1.5 g/kg GABA)。每周测量血糖。用 Western 印迹法评估蛋白质表达。用 H&E 和 Masson 染色法检测组织病理学变化:-结果:糖尿病大鼠胃组织中的 NOS1 表达水平降低,COX-2 和胰蛋白酶-1 蛋白表达水平升高。胰岛素和 GABA 治疗使 NOS1 和 COX-2 水平恢复到控制值。胰岛素治疗增加了糖尿病大鼠体内的 PI3K、Akt 和 p-Akt,降低了胰蛋白酶-1、PAR-1、PAR-2 和 PAR-3 的水平。胰岛素和 GABA 治疗后,GABAA 和 GABAB 受体水平恢复正常。结论:这些结果表明,GABA 通过作用于 GABA 受体可调节胰蛋白酶-1/PARs/Akt/COX-2 途径,从而改善糖尿病胃肠病的并发症。
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来源期刊
Doklady Biochemistry and Biophysics
Doklady Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
1.60
自引率
12.50%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.
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