Therapeutic Role of Beta-Aminobutyric Acid in Male Rats with Streptozotocin-Induced Diabetes: Insights into GIP, GLP-1, SCube1/2, Resistin, and Preproglucagon Gene Expression

Abstract

     Diabetes mellitus is a complex metabolic disorder characterized by hyperglycemia. This study aimed to evaluate the protective effect of beta-aminobutyric acid (BABA) on streptozotocin (STZ)-induced diabetes in male rats, by studying its impact on glucose-dependent insulinotropic polypeptide (GIP(, glucagon-like peptide-1 )GLP-1(, signal peptide, CUB and EGF-Like domain-containing protein  1/2 (SCube1/2), and Resistin (RETN) pathways. Thirty adult male rats with diabetes mellitus were randomly assigned to six groups of five rats each, aged 6-8 weeks. Healthy with weights (140 to 160 grams), positive control treated with 2ml normal saline, negative control groups treated only with streptozotocin, groups treated with 50, 100, 150, 200 mg/kg of streptozotocin (STZ), then BABA, respectively. β-aminobutyric acid was administered twice weekly via oral gavage for 30 days following STZ induction at varying concentrations across the groups. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate serum levels of GIP, GLP-1, SCUBE1 and SCUBE2, and RTN. The expression levels of the resistin (RES) gene and the preproglucagon (GCG) gene were assessed using the reverse transcription-quantitative polymerase chain reaction (qRT-PCR) technique. At the end of the experiment periods, blood was collected after overnight fasting. Triplicate technical sampling for all assays was studied. The results showed decreases in GIP, GLP-1, SCube ½, and RTN levels. Though treatment with BABA significantly enhanced those parameters, leading to elevated GIP and SCube 1/2 and reduced RTN, demonstrating a therapeutic effect that positively affects metabolic function. Group C1 treated with STZ followed by 150mg/kg BABA showed the highest GCG expression level (3.70635), which was significantly higher than that of other groups. On the other hand, A2 treated with STZ and 100 mg/kg BABA showed a decline in GCG expression with a fold change of 0.00458. Furthermore, the B1 and C1 groups displayed significantly higher RES expression levels (7.26015 and 3.09513, respectively) than the control groups. These findings support further investigation of BABA as a novel therapeutic compound for modulating metabolic and inflammatory pathways in type 2 diabetes