Gamma-Aminobutyric Acid Improves Insulin Sensitivity and Metabolic Profile in a Rat Model of Diet-Induced Insulin Resistance

Abstract

Prediabetes is characterized by elevated blood sugar levels that are not high enough to diagnose type 2 diabetes. It involves insulin resistance and impaired insulin secretion, which are often present before diagnosis. Prediabetes increases the risk of developing type 2 diabetes and cardiovascular disease. Disrupted insulin signaling in the brain can lead to neuronal dysfunction and impaired cognitive performance. This study aimed to test the hypothesis that gamma-aminobutyric acid (GABA) supplementation will improve insulin sensitivity in a rat model of T2DM. Rats were fed a high-fat diet to induce insulin resistance and T2DM. Rats meeting the diagnostic criteria for prediabetes were selected and divided into 3 groups: GABA supplementation, pathological control, and healthy control. GABA (200 mg/Kg body weight/day) was administered for 1 month. Fasting blood glucose, serum insulin, lipid profile, and HOMA-IR were measured at baseline, after diet-induction of T2DM, and after GABA treatment. GABA significantly reduced weight, blood glucose, serum insulin, HOMA-IR, triglycerides, cholesterol, LDL, and VLDL compared to pathological controls. GABA also increased HDL. Correlation analysis showed a significant positive association between HOMA-IR and weight, blood glucose, and serum insulin. The results suggest GABA supplementation improves insulin sensitivity, glycemic control, and lipid profile in a rat model of diet-induced T2DM. Proposed mechanisms include enhancing insulin signaling, increasing GLUT4 expression, promoting β-cell proliferation, and reducing oxidative stress through free radical scavenging. Further research on GABA's therapeutic potential in human T2DM patients is warranted.