The Potential Role of Pancreatic γ‑Aminobutyric Acid (GABA) in Diabetes Mellitus: A Critical Reappraisal

Hayder M. AlKuraishy, Nawar R. Hussian, Marwa S. Al-Naimi, Ali I. Al-Gareeb, Farah Al-Mamorri, Ali K. Al-Buhadily

Abstract


Background: Diabetes mellitus (DM) is an endocrine disorder characterized by hyperglycemia, polyuria, polydipsia, and glucosuria. γ‑aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central nervous system (CNS) of humans and other mammals. GABA acts on two different receptors, which are GABA‑A and GABA‑B. Pancreatic β‑cells synthesize GABA from glutamic acid by glutamic acid decarboxylase (GAD).

Aim: The objective of this study was to explore the potential role of pancreatic GABA on glycemic indices in DM.

Methods: Evidence from experimental, preclinical, and clinical studies are evaluated for bidirectional relationships between pancreatic GABA and blood glucose disorders. A multiplicity of search strategies took on and assumed included electronic database searches of Medline and Pubmed using MeSH terms, keywords and title words during the search.

Results: The pancreatic GABA signaling system has a role in the regulation of pancreatic hormone secretions, inhibition of immune response, improve β‑cells survival, and change α cell into β‑cell. Moreover, a GABA agonist improves the antidiabetic effects of metformin. In addition, benzodiazepine receptor agonists improve pancreatic β‑cell functions through GABA dependent pathway or through modulation of pancreatic adenosine and glucagon‑like peptide (GLP‑1).

Conclusions: Pancreatic GABA improves islet cell function, glucose homeostasis, and autoimmunity in DM. Orally administered GABA is safe for humans, and acts on peripheral GABA receptors and represents a new therapeutic modality for both T1DM and T2DM. Besides, GABA‑A receptor agonist like benzodiazepines improves pancreatic β‑cell function and insulin sensitivity through activation of GABA‑A receptors.


Keywords


Benzodiazepines; diabetes mellitus; gamma‑aminobutyric acid

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