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The maintenance of whole-body glucose homeostasis is critical for survival, and is controlled by the coordination of multiple organs and endocrine systems. Pancreatic islet β cells secrete insulin in response to nutrient stimuli, and insulin then travels through the circulation promoting glucose uptake into insulin-responsive tissues such as liver, skeletal muscle and adipose. Many of the genes identified in human genome-wide association studies of diabetic individuals are directly associated with β cell survival and function, giving credence to the idea that β-cell dysfunction is central to the development of type 2 diabetes. As such, investigations into the mechanisms by which β cells sense glucose and secrete insulin in a regulated manner are a major focus of current diabetes research. In particular, recent discoveries of the detailed role and requirements for reorganization/remodeling of filamentous actin (F-actin) in the regulation of insulin release from the β cell have appeared at the forefront of islet function research, having lapsed in prior years due to technical limitations. Recent advances in live-cell imaging and specialized reagents have revealed localized F-actin remodeling to be a requisite for the normal biphasic pattern of nutrient-stimulated insulin secretion. This review will provide an historical look at the emergent focus on the role of the actin cytoskeleton and its regulation of insulin secretion, leading up to the cutting-edge research in progress in the field today. Nutrient-induced remodeling of the actin cytoskeletal network fine-tunes the amount of insulin secreted by pancreatic islet beta cells. In a review article, molecular biologists Michael Kalwat of the University of Texas Southwestern Medical Center in Dallas, and Debbie Thurmond of Indiana University School of Medicine in Indianapolis, discuss how the structure of filamentous actin (F-actin) affects both basal insulin levels and glucose-stimulated insulin release. Thanks to recent advances in live-cell and time-lapse imaging, scientists have teased apart several of the signaling pathways and actin-binding proteins that affect the reorganization of F-actin. Kalwat and Thurmond note that a better understanding of the mechanisms by which F-actin helps beta cells to sense glucose and secrete insulin in a regulated manner should lead to new treatments for diabetes.
Kalwat et al. (Thu,) studied this question.