The beneficial effect of gamma aminobutyric acid on diabetic nephropathy in type 2 diabetic rat model and their offspring.

Background and purpose: Diabetic nephropathy (DN) in the first and second generations of diabetic rats and improving kidney function by gamma aminobutyric acid (GABA) were investigated.

Experimental approach: Male and female rats and their offspring were used. Diabetes was induced by a high-fat diet and a low dose of streptozotocin. Animals were divided into the diabetic positive control (D) group, the diabetic group receiving insulin (D + insulin), and the diabetic group receiving GABA (D + GABA). In addition, two groups of non-diabetic parents were assigned as negative control (NDC) groups. Each animal was monitored for 16 weeks, and offspring were fed with normal diet. The blood glucose level, urine volume, and water intake, as well as renal function, including the serum levels of blood urea nitrogen (BUN), creatinine (Cr), and glomerular filtration rate (GFR) were assessed. Also, the hyperinsulinemic-euglycemic clamp and gene expressions of Nox4 and Icaml in the kidneys were measured for all subjects.

Findings/results: GABA administration in parents and offspring decreased blood glucose level, insulin resistance, GFR, serum levels of BUN and Cr compared to the D groups. GABA reduced the urine Cr, BUN, and albumin loads in both parents and offspring in comparison to the D groups. GABA decreased Nox4 and Icaml gene expression in both parents and offspring.

Conclusion and implications: GABA decreased the risk of DN, hyperglycemia, and insulin resistance in both diabetic parents and their offspring by improving kidney function, highlighting the potential therapeutic benefits of GABA in managing type 2 diabetes complications.