Abstract
Background Gamma-aminobutyric acid (GABA) and magnesium sulfate (MgSO4) play a crucial role in glycemic control. Therefore, we studied the effect of combination therapy with GABA and MgSO4 to improve insulin sensitivity in diabetes induced by streptozotocin as well as high-fat diet in a diabetic rat model. Design and Methods. Forty randomly selected rats were assigned to four groups: nondiabetic control group was fed the normal diet, insulin-resistant diabetic rat model was induced by streptozotocin and high-fat diet, GABA + MgSO4 group received GABA and MgSO4, and insulin group was treated with insulin. Body weight, abdominal fat, blood glucose, serum insulin, and glucagon concentration were measured. The glucose clamp technique, glucose tolerance test, and insulin tolerance test were performed to study insulin sensitivity. Also, the expressions of glucose 6 phosphatase, glucagon receptor, and phosphoenolpyruvate carboxykinase genes in liver were assessed for the gluconeogenesis pathway. Protein translocation and glucose transporter 4 (Glut4) genes expression in muscle were also assessed. Results Combination of GABA + MgSO4 or insulin therapy enhanced insulin level, glycemic control, glucose and insulin tolerance test, some enzymes expression in the gluconeogenesis pathway, body fat, body weight, and glucagon receptor in diabetic rats. Moreover, an increase was observed in protein and gene expression of Glut4. Insulin sensitivity in combination therapy was more than the insulin group. Conclusions GABA and MgSO4 enhanced insulin sensitivity via increasing Glut4 and reducing the gluconeogenesis enzyme and glucagon receptor gene expressions.
Highlights
World Health Organization (WHO) announced that, by 2030, diabetes is going to be the seventh major cause of mortality [1]
Hyperglycemia as one of diabetes pathogenesis is caused by several factors such as impaired insulin secretion, or PI3/AKT signaling [2], which leads to the impairment of the insulin-dependent glucose transporter 4 (Glut4) in muscles and the utilization of glucose decreases which is called peripheral insulin resistance [3, 4]
Rats with high-fat diet (HFD) were injected with 35 mg/kg of streptozotocin (STZ) intraperitoneally (I.P) (Sigma Aldrich, Hamburg, Germany) and rats in the control group received normal saline. ree days later, we sued type 2 diabetes mellitus (T2DM) models for groups of animals that had fed blood glucose level greater than 250 mg/dl for three successive days and they were fed with the same individual diets up to 12 weeks (HFD: 4920 vs. 3100 Kcal/kg)
Summary
World Health Organization (WHO) announced that, by 2030, diabetes is going to be the seventh major cause of mortality [1]. Hyperglycemia as one of diabetes pathogenesis is caused by several factors such as impaired insulin secretion, or PI3/AKT signaling [2], which leads to the impairment of the insulin-dependent glucose transporter 4 (Glut4) in muscles and the utilization of glucose decreases which is called peripheral insulin resistance [3, 4] Another important pathophysiology of diabetes is increasing glucagon secretion despite hyperglycemia [5]. Combination of GABA + MgSO4 or insulin therapy enhanced insulin level, glycemic control, glucose and insulin tolerance test, some enzymes expression in the gluconeogenesis pathway, body fat, body weight, and glucagon receptor in diabetic rats. GABA and MgSO4 enhanced insulin sensitivity via increasing Glut and reducing the gluconeogenesis enzyme and glucagon receptor gene expressions
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