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.

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.