Targeting GABA signaling in type 1 diabetes and its complications- an update on the state of the art.

Abstract

Type 1 diabetes (T1D) is an autoimmune disease that leads to the progressive destruction of insulin-producing β cells, resulting in lifelong insulin dependence and a range of severe complications. Beyond conventional glycemic control, innovative therapeutic strategies are needed to address the underlying disease mechanisms. Recent research has highlighted gamma-aminobutyric acid (GABA) as a promising therapeutic target for T1D due to its dual role in modulating both β cell survival and immune response within pancreatic islets. GABA signaling supports β cell regeneration, inhibits α cell hyperactivity, and promotes α-to-β cell transdifferentiation, contributing to improved islet function. Moreover, GABA's influence extends to mitigating T1D complications, including nephropathy, neuropathy, and retinopathy, as well as regulating central nervous system pathways involved in glucose metabolism. This review consolidates the latest advances in GABA-related T1D therapies, covering animal preclinical and human clinical studies and examining the therapeutic potential of GABA receptor modulation, combination therapies, and dietary interventions. Emphasis is placed on the translational potential of GABA-based approaches to enhance β cell viability and counteract autoimmune processes in T1D. Our findings underscore the therapeutic promise of GABA signaling modulation as a novel approach for T1D treatment and encourage further investigation into this pathway's role in comprehensive diabetes management.