The Role of GABA and Insulin Regulated Aminopeptidase on Insulin Resistance and GLUT4 in Prediabetes and Type 2 Diabetes Mellitus

Abstract

Background: Different proposed mechanisms for insulin resistance have been put forth to understand the relationship and changes in insulin resistance. Looking at the levels of insulin, the neurotransmitter gamma-aminobutyric acid, glucose transport type 4, and the newly discovered enzyme insulin regulated aminopeptidase may provide an integrated perspective on insulin resistance. Objectives: To study the role of serum gamma-aminobutyric acid and insulin regulated aminopeptidase enzyme levels in pathogenesis of insulin resistance and translocation of glucose transport type 4 in patients with type2 diabetes mellitus and pre-diabetes ones. Subjects and methods: Ninety individuals were divided into three age- and BMI matched groups (diabetics, prediabetics, healthy) were assessed for glycated hemoglobin (turbidometry method), fasting serum glucose (colorimetric method), serum insulin (electrochemiluminescence immunoassay method), homeostatic model assessment for insulin resistance, serum gamma-aminobutyric acid, glucose transporter type 4, and insulin regulated aminopeptidase measured by the sandwich ELISA method. The cut-off value was adopted according to the World Health Organization, individuals with their fasting serum glucose lower than 110 mg/ml, and glycated hemoglobin level not more than 5.7 % are considered healthy individuals. Result: The mean (±SD) values of serum insulin regulated aminopeptidase, gamma-aminobutyric acid and glucose transport type 4 showed significantly lower levels with greater increases in insulin resistance, represented by the significant decrease in diabetics group who have high insulin resistance compared with pre-diabetics and healthy individuals’ groups (p < 0.05). They also significantly decrease in individuals with the pre-diabetic stage compared to healthy individuals without insulin resistance (p < 0.05). Significant negative correlations were found between HOMA-IR values and each of GABA, IRAP, and GLUT4. Conclusion: Decreasing gamma-aminobutyric acid may promote insulin resistance and prediabetes/diabetes onset. Decreased insulin regulated aminopeptidase levels suggest a role alongside glucose transport type 4 in glucose uptake, allowing screening for prediabetes risk.