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Involvement of Γ-Aminobutyric Acid and N-Methyl-D-Aspartate Receptors in Diabetic Gastropathy in Rats: Possible Beneficial Effect of Prolonged Treatment With Insulin and Magnesium Supplement Publisher Pubmed



Saberi H1 ; Mehranfard N2 ; Rezazadeh H3 ; Ghasemi M3
Authors
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Authors Affiliations
  1. 1. School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Nanokadeh Darooee Samen Private Joint Stock Company, Urmia, 5715793731, Iran
  3. 3. Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Archives of Razi Institute Published:2024


Abstract

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. Copyright © 2023.
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