Long-Term Gaba Supplementation Regulates Diabetic Gastroenteropathy Through Gaba Receptor/Trypsin-1/Pars/Akt/Cox-2 Axis Publisher Pubmed



Yazdanimoghaddam F¹ ; Rezazadeh H² ; Soltani N² ; Mehranfard N³ ; Dastgerdi AH⁴ ; Rad MG⁵ ; Ghasemi M²
Source: Doklady Biochemistry and Biophysics Published:2024

Abstract

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). 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. © Pleiades Publishing, Ltd. 2024. ISSN 1607-6729, Doklady Biochemistry and Biophysics, 2024, Vol. 518, pp. 452–462. Pleiades Publishing, Ltd., 2024. ISSN 1607-6729, Doklady Biochemistry and Biophysics, 2024. Pleiades Publishing, Ltd., 2024.