1-Integrin--A Key Player in Controlling Pancreatic Beta-Cell Insulin Secretion via Interplay With SNARE Proteins

• Published in: Endocrinology (Philadelphia) 2023-01, Vol.164 (1), p.1
• Main Authors: Barillaro, Malina, Schuurman, Meg, Wang, Rennian
• Format: Article
• Language: English
• Subjects: Dextrose; Diabetes therapy; Diabetics; Glucose; Insulin; Integrins; Muscle proteins
• ISSN: 0013-7227
• DOI: 10.1210/endocr/bqac179

Shortcomings in cell-based therapies for patients with diabetes have been revealed to be, in part, a result of an improper extracellular matrix (ECM) environment. In vivo, pancreatic islets are emersed in a diverse ECM that provides physical support and is crucial for healthy function. [beta]1-Integrin receptors have been determined to be responsible for modulation of beneficial interactions with ECM proteins influencing betacell development, proliferation, maturation, and function. [beta]1-Integrin signaling has been demonstrated to augment insulin secretion by impacting the actin cytoskeleton via activation of focal adhesion kinase and downstream signaling pathways. In other secretory cells, evidence of a bidirectional relationship between integrins and exocytotic machinery has been demonstrated, and, thus, this relationship could be present in pancreatic beta cells. In this review, we will discuss the role of ECM-[beta]1-integrin interplay with exocytotic proteins in controlling pancreatic beta-cell insulin secretion through their dynamic and unique signaling pathway. Key Words: beta cell, [beta]1 integrin, insulin secretion, SNARE proteins, actin cytoskeleton, FAK signaling Abbreviations: BAG3, BCL-2-associated athanogene 3; BM, basement membrane; Cdc42, cell division control protein 42; ECM, extracellular matrix; ERK1/2, extracellular signal-regulated kinases 1/2; FAK, focal adhesion kinase; GSIS, glucose-stimulated insulin secretion; KO, knockout; PDX, pancreatic and duodenal homeobox; PM, plasma membrane; Rac1, Ras-related C3 botulinum toxin substrate 1; SG, secretory granule; SNAP, synaptosomal-associated protein; SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptor; VAMP, vesicle associated membrane protein.