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

• Published in: Doklady. Biochemistry and biophysics 2024-10, Vol.518 (1), p.452-462
• Main Authors: Yazdanimoghaddam, Farzaneh, Rezazadeh, Hossein, Soltani, Nepton, Mehranfard, Nasrin, Dastgerdi, Azadesadat Hosseini, Rad, Mahtab Ghanbari, Ghasemi, Maedeh
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Diabetes; Diabetes mellitus; High fat diet; Insulin; Life Sciences; Molecular Biology; Nitric-oxide synthase; Protein expression; Proteinase-activated receptor 1; Proteins; Streptozocin; Trypsin; Western blotting; γ-Aminobutyric acid A receptors; γ-Aminobutyric acid B receptors; γ-Aminobutyric acid receptors
• ISSN: 1607-6729; 1608-3091; 1608-3091
• DOI: 10.1134/S1607672924600386

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). Method 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. Results 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. Conclusion 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.