Alpha cells as targets for incretin therapy

Abstract

Abstract The pivotal role of alpha cells in glucose homeostasis, primarily through glucagon secretion, necessitates a deeper understanding of their potential as therapeutic targets in diabetes management. This narrative review explores the emerging paradigm of incretin-based therapies targeting alpha cells to ameliorate hyperglycemia associated with diabetes. Amidst the prevailing focus on beta cells, this review accentuates the lesser-explored potential of alpha cells in modulating glucose levels. Incretin hormones, notably glucagon-like peptide-1 (GLP-1), not only augment insulin secretion but also inhibit glucagon release, thereby acting as a dual mechanism for glucose control. Contemporary pharmaceutical agents like GLP-1 receptor agonists and DPP-4 inhibitors exhibit promise in modulating alpha-cell function, with evidence suggesting their efficacy in reducing postprandial glucagon and improving glycemic control. Clinical trials evince a favorable safety profile with minimal hypoglycemia risk. Moreover, DPP-4 inhibitors demonstrate a unique potential in reducing glycemic variability by nuanced modulation of alpha-cell activity. This review underscores the imperative for further research to elucidate the molecular pathways underpinning alpha-cell dysfunction in diabetes and to explore combinatory regimens for optimizing glycemic control. The insights garnered could pave the way for novel therapeutic strategies, enriching the armamentarium against diabetes through a more holistic approach targeting both alpha and beta cells.