The skeleton in the closet: actin cytoskeletal remodeling in β-cell function

Abstract

Over the last few decades, biomedical research has considered not only the function of single cells but also the importance of the physical environment within a whole tissue, including cell-cell and cell-extracellular matrix interactions. Cytoskeleton organization and focal adhesions are crucial sensors for cells that enable them to rapidly communicate with the physical extracellular environment in response to extracellular stimuli, ensuring proper function and adaptation. The involvement of the microtubular-microfilamentous cytoskeleton in secretion mechanisms was proposed almost 50 years ago, since when the evolution of ever more sensitive and sophisticated methods in microscopy and in cell and molecular biology have led us to become aware of the importance of cytoskeleton remodeling for cell shape regulation and its crucial link with signaling pathways leading to β-cell function. Emerging evidence suggests that dysfunction of cytoskeletal components or extracellular matrix modification influences a number of disorders through potential actin cytoskeleton disruption that could be involved in the initiation of multiple cellular functions. Perturbation of β-cell actin cytoskeleton remodeling could arise secondarily to islet inflammation and fibrosis, possibly accounting in part for impaired β-cell function in type 2 diabetes. This review focuses on the role of actin remodeling in insulin secretion mechanisms and its close relationship with focal adhesions and myosin II.

The biomechanical properties of an epithelial tissue determine the location of its vasculature

“…Since non-muscle myosin II isoforms are expressed in endocrine pancreatic cells56, and since, to our knowledge, the role of ILK in cell cortex tension has not yet been studied, we measured cortical tension in control versus ILK-silenced islet cells. To this end, we deformed the surface of dissociated pancreatic endocrine cells with a colloidal force probe and recorded force-indentation curves required for deformation (Fig.…”

Role and impact of the extracellular matrix on integrin‐mediated pancreatic β‐cell functions

“…These functions critically depend on where the actin filaments are localised in the cell (centre or periphery) (see (Kalwat and Thurmond, ) and also discussed in Arous et al. () and Arous and Halban (). The barrier or rail function of F‐actin appears also to depend on the remodelling of FAs, the specific actin isoform involved, or which motor protein is associated with the F‐actin structures.…”

GPR40-Mediated Gα12 Activation by Allosteric Full Agonists Highly Efficacious at Potentiating Glucose-Stimulated Insulin Secretion in Human Islets

“…Although other agonists should be evaluated in this assay, these data suggest that the ability to activate Ga12 is a unique property of synthetic allosteric full agonists. The role of the Ga12/13 pathway in insulin and incretin secretion is poorly understood but it has been linked to PKD activation as well as actin remodeling, well known to contribute to vesicle release (Siehler, 2007;Ferdaoussi et al, 2012;Kalwat and Thurmond, 2013;Arous and Halban, 2015). Insulin secretion in response to glucose is biphasic, with a rapid and transient first phase followed by a slower but prolonged second phase.…”