Sushant Bhatnagar, Ph.D.
Sushant Bhatnagar, Ph.D., Associate Professor in the UAB Division of Endocrinology, Diabetes, and Metabolism, has published an extensive review in Comprehensive Physiology, a peer-reviewed journal of the American Physiological Society, offering new insights into the cell-specific roles of BAI receptors in health and metabolic disorders.
G protein–coupled receptors (GPCRs) are among the most extensively studied signaling proteins in biology and remain the most commonly targeted drug class. Yet adhesion-type GPCRs (aGPCRs), and within them the brain-specific angiogenesis inhibitor (BAI/ADGRB) subfamily, remain among the least well understood. Emerging research suggests that BAI receptors are integral to diverse biological processes, and their dysfunction has been linked to cancer, neurodevelopmental disorders, and metabolic diseases, including Type 2 diabetes (T2D).
In their review, “Cell-Specific Functions of the BAI/ADGRB Subfamily of Adhesion G-Protein-Coupled Receptors,” Bhatnagar and postdoctoral fellow Haifa Alsharif, Ph.D., summarize current understanding of how BAI1, BAI2, and BAI3 function across multiple physiological systems, from the brain to metabolic tissues.
“Although recent research has started to uncover the roles of BAI receptors in energy balance and metabolism, their functions in glucose homeostasis and metabolic disease are still not fully understood,” said Bhatnagar.
The review highlights how altered G-protein signaling in metabolic tissues contributes to impaired glucose tolerance, insulin resistance, and energy expenditure, underscoring the importance of dissecting the contributions of adhesion GPCRs, particularly the BAI subfamily, in energy metabolism and systemic glucose regulation.
Bhatnagar’s work provides fresh perspectives on how BAI receptors may influence insulin sensitivity, synaptic connectivity, and tissue regeneration, revealing their potential as therapeutic targets for metabolic disorders such as obesity and T2D.
“Taken together, BAI/ADGRBs exemplify the multifunctionality of adhesion GPCRs, operating at the crossroads of immune surveillance, synaptic connectivity, energy homeostasis, and tissue regeneration,” said Bhatnagar. “As tools for structural biology, cell-type–specific profiling, and pharmacological manipulation advance, the coming decade is poised to bring transformative insights into how BAI receptors orchestrate physiology. Ultimately, translating these insights into therapeutic strategies may open new avenues for treating neuropsychiatric disorders, metabolic disease, infertility, and cancer.”
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK120684- 01, 1R21DK129968-01, 4R00DK095975- 03, 5P30DK079626-10) and American Diabetes Association (1-18-PDF-103).
Read the full review in the December 2025 issue of Comprehensive Physiology.