β1 integrin is a crucial regulator of pancreatic β-cell expansion

Abstract

SUMMARYDevelopment of the endocrine compartment of the pancreas, as represented by the islets of Langerhans, occurs through a series of highly regulated events encompassing branching of the pancreatic epithelium, delamination and differentiation of islet progenitors from ductal domains, followed by expansion and three-dimensional organization into islet clusters. Cellular interactions with the extracellular matrix (ECM) mediated by receptors of the integrin family are postulated to regulate key functions in these processes. Yet, specific events regulated by these receptors in the developing pancreas remain unknown. Here, we show that ablation of the β1 integrin gene in developing pancreatic β-cells reduces their ability to expand during embryonic life, during the first week of postnatal life, and thereafter. Mice lacking β1 integrin in insulin-producing cells exhibit a dramatic reduction of the number of β-cells to only ~18% of wild-type levels. Despite the significant reduction in β-cell mass, these mutant mice are not diabetic. A thorough phenotypic analysis of β-cells lacking β1 integrin revealed a normal expression repertoire of β-cell markers, normal architectural organization within islet clusters, and a normal ultrastructure. Global gene expression analysis revealed that ablation of this ECM receptor in β-cells inhibits the expression of genes regulating cell cycle progression. Collectively, our results demonstrate that β1 integrin receptors function as crucial positive regulators of β-cell expansion.

Epithelial cell integrin β1 is required for developmental angiogenesis in the pituitary gland

“…Our findings provide unambiguous evidence of critical non-cellautonomous roles for integrin β1 in vascular development that contrast with numerous reports of other tissue-specific integrin β1 knockouts (31)(32)(33)(34), and complement established vascular cellautonomous functions of integrin β1 (9-13). Our data support the idea that there are distinct tissue and temporal context-dependent requirements for specific integrin heterodimers in vascular development (11).…”

Nrf2/antioxidant pathway mediates β cell self-repair after damage by high-fat diet–induced oxidative stress

“…Ultrastructural analysis on pancreatic islets from control, HFD, and diet-reversed ZDF animals was performed by TEM, as previously described with minor modifications (44)(45)(46). Briefly, islets were fixed immediately after isolation at 4°C in 0.1 M sodium cacodylate buffer, pH 7.4, 2% paraformaldehyde, 2.5% glutaraldehyde (Electron Microscopy Sciences), and 3 μM CaCl 2 .…”

Functionalized self-assembling peptide improves INS-1 β-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway

“…6 Integrin β1 is the major receptor of type I and IV collagen, and has been shown to regulate development and function of the pancreas. 32 Integrin α5β1 is the primary receptor for fibronectin and is involved in cell adhesion, migration, and ECM formation. 33 We observed increased integrin α5 and β1 in the KLD-F group, suggesting that KLD-F can interact with multiple integrins and thereby trigger downstream pathways in the β-cell.…”