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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
Authors
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Authors Affiliations
  1. 1. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 4631-19395, Iran
  2. 2. Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Nanokadeh Darooee Samen, Private Joint Stock Company, Urmia, 5715793731, Iran
  4. 4. Clinical Research Development Center, Najafabad Branch, Islamic Azad University, Najafabad, Iran
  5. 5. Gerash Cellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash, Iran

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.
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